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1. Designing, Developing, and Testing a Chatbot for Parents and Caregivers of Children and Young People With Rheumatological Conditions (the IMPACT Study): Protocol for a Co-Designed Proof-of-Concept Study

Author: Polly Livermore, Klaudia Kupiec, Lucy R Wedderburn, Andrea Knight, Ameenat L Solebo, Roz Shafran, Glenn Robert, N J Sebire, and Faith Gibson
Subjects: Medicine, Computer applications to medicine. Medical informatics, R858-859.7
Abstract: BackgroundPediatric rheumatology is a term that encompasses over 80 conditions affecting different organs and systems. Children and young people with rheumatological chronic conditions are known to have high levels of mental health problems and therefore are at risk of poor health outcomes. Clinical psychologists can help children and young people manage the daily difficulties of living with one of these conditions; however, there are insufficient pediatric psychologists in the United Kingdom. We urgently need to consider other ways of providing early, essential support to improve their current well-being. One way of doing this is to empower parents and caregivers to have more of the answers that their children and young people need to support them further between their hospital appointments. ObjectiveThe objective of this co-designed proof-of-concept study is to design, develop, and test a chatbot intervention to support parents and caregivers of children and young people with rheumatological conditions. MethodsThis study will explore the needs and views of children and young people with rheumatological conditions, their siblings, parents, and caregivers, as well as health care professionals working in pediatric rheumatology. We will ask approximately 100 participants in focus groups where they think the gaps are in current clinical care and what ideas they have for improving upon them. Creative experience-based co-design workshops will then decide upon top priorities to develop further while informing the appearance, functionality, and practical delivery of a chatbot intervention. Upon completion of a minimum viable product, approximately 100 parents and caregivers will user-test the chatbot intervention in an iterative sprint methodology to determine its worth as a mechanism for support for parents. ResultsA total of 73 children, young people, parents, caregivers, and health care professionals have so far been enrolled in the study, which began in November 2023. The anticipated completion date of the study is April 2026. The data analysis is expected to be completed in January 2026, with the results being published in April 2026. ConclusionsThis study will provide evidence on the accessibility, acceptability, and usability of a chatbot intervention for parents and caregivers of children and young people with rheumatological conditions. If proven useful, it could lead to a future efficacy trial of one of the first chatbot interventions to provide targeted and user-suggested support for parents and caregivers of children with chronic health conditions in health care services. This study is unique in that it will detail the needs and wants of children, young people, siblings, parents, and caregivers to improve the current support given to families living with pediatric rheumatological conditions. It will be conducted across the whole of the United Kingdom for all pediatric rheumatological conditions at all stages of the disease trajectory. International Registered Report Identifier (IRRID)DERR1-10.2196/57238
Published: 2024
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2. Towards stratified treatment of JIA: machine learning identifies subtypes in response to methotrexate from four UK cohortsResearch in context

Author: Stephanie J.W. Shoop-Worrall, Saskia Lawson-Tovey, Lucy R. Wedderburn, Kimme L. Hyrich, Nophar Geifman, Aline Kimonyo, Alyssia McNeece, Andrew Dick, Andrew Morris, Annie Yarwood, Athimalaipet Ramanan, Bethany R. Jebson, Chris Wallace, Daniela Dastros-Pitei, Damian Tarasek, Elizabeth Ralph, Emil Carlsson, Emily Robinson, Emma Sumner, Fatema Merali, Fatjon Dekaj, Helen Neale, Hussein Al-Mossawi, Jacqui Roberts, Jenna F. Gritzfeld, Joanna Fairlie, John Bowes, John Ioannou, Melissa Kartawinata, Melissa Tordoff, Michael Barnes, Michael W. Beresford, Michael Stadler, Paul Martin, Rami Kallala, Sandra Ng, Samantha Smith, Sarah Clarke, Soumya Raychaudhuri, Stephen Eyre, Sumanta Mukherjee, Teresa Duerr, Thierry Sornasse, Vasiliki Alexiou, Victoria J. Burton, Wei-Yu Lin, Wendy Thomson, and Zoe Wanstall
Subjects: Juvenile idiopathic arthritis, Machine learning, Treatment outcome, Epidemiology, Methotrexate, Medicine, Medicine (General), R5-920
Abstract: Summary: Background: Methotrexate (MTX) is the gold-standard first-line disease-modifying anti-rheumatic drug for juvenile idiopathic arthritis (JIA), despite only being either effective or tolerated in half of children and young people (CYP). To facilitate stratified treatment of early JIA, novel methods in machine learning were used to i) identify clusters with distinct disease patterns following MTX initiation; ii) predict cluster membership; and iii) compare clusters to existing treatment response measures. Methods: Discovery and verification cohorts included CYP who first initiated MTX before January 2018 in one of four UK multicentre prospective cohorts of JIA within the CLUSTER consortium. JADAS components (active joint count, physician (PGA) and parental (PGE) global assessments, ESR) were recorded at MTX start and over the following year.Clusters of MTX ‘response’ were uncovered using multivariate group-based trajectory modelling separately in discovery and verification cohorts. Clusters were compared descriptively to ACR Pedi 30/90 scores, and multivariate logistic regression models predicted cluster-group assignment. Findings: The discovery cohorts included 657 CYP and verification cohorts 1241 CYP. Six clusters were identified: Fast improvers (11%), Slow Improvers (16%), Improve-Relapse (7%), Persistent Disease (44%), Persistent PGA (8%) and Persistent PGE (13%), the latter two characterised by improvement in all features except one. Factors associated with clusters included ethnicity, ILAR category, age, PGE, and ESR scores at MTX start, with predictive model area under the curve values of 0.65–0.71. Singular ACR Pedi 30/90 scores at 6 and 12 months could not capture speeds of improvement, relapsing courses or diverging disease patterns. Interpretation: Six distinct patterns following initiation of MTX have been identified using methods in artificial intelligence. These clusters demonstrate the limitations in traditional yes/no treatment response assessment (e.g., ACRPedi30) and can form the basis of a stratified medicine programme in early JIA. Funding: Medical Research Council, Versus Arthritis, Great Ormond Street Hospital Children's Charity, Olivia’s Vision, and the National Institute for Health Research.
Published: 2024
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3. The successes and challenges of harmonising juvenile idiopathic arthritis (JIA) datasets to create a large-scale JIA data resource

Author: Saskia Lawson-Tovey, Samantha Louise Smith, Nophar Geifman, Stephanie Shoop-Worrall, Sandra Ng, Michael R. Barnes, Lucy R. Wedderburn, Kimme L. Hyrich, and CLUSTER consortium
Subjects: Data harmonisation, Children and young people, JIA, Pediatrics, RJ1-570, Diseases of the musculoskeletal system, RC925-935
Abstract: Abstract Background CLUSTER is a UK consortium focussed on precision medicine research in JIA/JIA-Uveitis. As part of this programme, a large-scale JIA data resource was created by harmonizing and pooling existing real-world studies. Here we present challenges and progress towards creation of this unique large JIA dataset. Methods Four real-world studies contributed data; two clinical datasets of JIA patients starting first-line methotrexate (MTX) or tumour necrosis factor inhibitors (TNFi) were created. Variables were selected based on a previously developed core dataset, and encrypted NHS numbers were used to identify children contributing similar data across multiple studies. Results Of 7013 records (from 5435 individuals), 2882 (1304 individuals) represented the same child across studies. The final datasets contain 2899 (MTX) and 2401 (TNFi) unique patients; 1018 are in both datasets. Missingness ranged from 10 to 60% and was not improved through harmonisation. Conclusions Combining data across studies has achieved dataset sizes rarely seen in JIA, invaluable to progressing research. Losing variable specificity and missingness, and their impact on future analyses requires further consideration.
Published: 2023
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4. JAK inhibitors: a potential treatment for JDM in the context of the role of interferon-driven pathology

Author: Meredyth G. Ll Wilkinson, Claire T. Deakin, Charalampia Papadopoulou, Despina Eleftheriou, and Lucy R. Wedderburn
Subjects: Juvenile dermatomyositis, JDM, IIM, JAK inhibitors, IFN, JAK/STAT pathway, Pediatrics, RJ1-570, Diseases of the musculoskeletal system, RC925-935
Abstract: Abstract Juvenile Idiopathic Inflammatory Myopathies (IIM) are a group of rare diseases that are heterogeneous in terms of pathology that can include proximal muscle weakness, associated skin changes and systemic involvement. Despite options for treatment, many patients continue to suffer resistant disease and lasting side-effects. Advances in the understanding of the immunopathology and genetics underlying IIM may specify new therapeutic targets, particularly where conventional treatment has not achieved a clinical response. An upregulated type I interferon signature is strongly associated with disease and could be a prime target for developing more specific therapeutics. There are multiple components of the IFN pathway that could be targeted for blockade therapy. Downstream of the cytokine receptor complexes are the Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway, which consists of JAK1–3, TYK2, and STAT1–6. Therapeutic inhibitors have been developed to target components of this pathway. Promising results have been observed in case studies reporting the use of the JAK inhibitors, Baricitinib, Tofacitinib and Ruxolitinib in the treatment of refractory Juvenile Dermatomyositis (JDM). There is still the question of safety and efficacy for the use of JAK inhibitors in JDM that need to be addressed by clinical trials. Here we review the future for the use of JAK inhibitors as a treatment for JDM.
Published: 2021
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5. The Effects of a Web-Based Tool for Parents of Children With Juvenile Idiopathic Arthritis: Randomized Controlled Trial

Author: Kathleen Mulligan, Shashivadan P Hirani, Sally Harris, Jo Taylor, Lucy R Wedderburn, and Stanton Newman
Subjects: Computer applications to medicine. Medical informatics, R858-859.7, Public aspects of medicine, RA1-1270
Abstract: BackgroundJuvenile idiopathic arthritis (JIA) is a group of autoinflammatory diseases that cause pain and disability if not controlled by treatment. Parenting a child with JIA is stressful for parents, who express concerns about their child’s treatment and may experience anxiety and powerlessness concerning their child’s illness. Parenting stress is greater in parents of children with chronic illness than in those with healthy children and is related to poorer psychological adjustment in both parents and children. It is therefore important to develop interventions to support parents. This paper reports the evaluation of a web-based tool that provides information and practical skills to help increase parents’ confidence in managing their child’s illness and reduce parenting stress. ObjectiveThe aim of this study is to evaluate the benefits of a web-based tool (WebParC) for parents of children with recently diagnosed JIA. MethodsA multicentered randomized controlled trial was conducted at pediatric rheumatology centers in England. We recruited parents of children aged ≤12 years who had been diagnosed with JIA within the previous 6 months. They were randomized to the intervention (WebParC access plus standard care) or the control (standard care alone) and followed up 4 months and 12 months after randomization. Where both parents participated, they were randomized by household to the same trial arm. The WebParC intervention consists of information about JIA and its treatment plus a toolkit, based on cognitive behavioral therapy, to help parents develop skills to manage JIA-related issues. The primary outcome was the self-report Pediatric Inventory for Parents measure of illness-related parenting stress. The secondary outcomes were parental mood, self-efficacy, coping, effectiveness of participation in their child’s health care, satisfaction with health care, and child’s health-related quality of life. ResultsA total of 203 households comprising 220 parents were randomized to the intervention (100/203, 49.3%) or control (103/203, 50.7%) arm. Follow-up assessments were completed by 65.5% (133/203) of the households at 4 months (intervention 60/100, 60%, and control 73/103, 70.9%) and 61.1% (124/203) of the households at 12 months (intervention 58/100, 58%, and control 66/103, 64.1%). A main effect of the trial arm was found on the Pediatric Inventory for Parents: the intervention participants reported less frequency (subscales communication F1,120627=5.37; P=.02, and role function F1,27203=5.40; P=.02) and difficulty (subscales communication F1,2237=7.43; P=.006, medical care F1,2907=4.04; P=.04, and role function F1,821=4.37, P=.04) regarding illness-related stressful events than the control participants. ConclusionsThe WebParC website for parents of children with JIA reduced illness-related parenting stress. This web-based intervention offers a feasible preventive approach for parents of children with JIA and potentially could be adapted and evaluated for parents of children with other chronic illnesses. Trial RegistrationInternational Standard Randomized Controlled Trial Number (ISRCTN) 13159730; http://www.isrctn.com/ISRCTN13159730
Published: 2022
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6. Male sex identified by global COVID-19 meta-analysis as a risk factor for death and ITU admission

Author: Hannah Peckham, Nina M. de Gruijter, Charles Raine, Anna Radziszewska, Coziana Ciurtin, Lucy R. Wedderburn, Elizabeth C. Rosser, Kate Webb, and Claire T. Deakin
Subjects: Science
Abstract: Anecdotal reports suggest potential severity and outcome differences between sexes following infection by SARS-CoV-2. Here, the authors perform meta-analyses of more than 3 million cases collected from global public data to demonstrate that male patients with COVID-19 are 3 times more likely to require intensive care, and have ~40% higher death rate.
Published: 2020
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7. Retrospective analysis of infliximab and adalimumab treatment in a large cohort of juvenile dermatomyositis patients

Author: Raquel Campanilho-Marques, Claire T. Deakin, Stefania Simou, Charalampia Papadopoulou, Lucy R. Wedderburn, Clarissa A. Pilkington, and for the Juvenile Dermatomyositis Research Group (JDRG)
Subjects: Infliximab, Adalimumab, Juvenile dermatomyositis, Biologic therapy, P rheumatology, Diseases of the musculoskeletal system, RC925-935
Abstract: Abstract Background Anti-TNF treatment may be useful for the treatment of patients with refractory juvenile dermatomyositis (JDM). The aim of this study was to describe the use of infliximab and adalimumab therapy in juvenile dermatomyositis as an adjunctive treatment. Methods Sixty children recruited to the UK JDM Cohort and Biomarker Study that had received at least 3 months of anti-TNF treatment (infliximab or adalimumab) were studied. Childhood Myositis Assessment Scale (CMAS), Manual Muscle Testing (MMT8) and physician’s global assessment (PGA) were recorded. Skin disease was assessed using the modified skin disease activity score (DAS). Data were analysed using Friedman’s test for repeated measures analysis of variance. Results Compared to baseline, there were improvements at 6 and 12 months in skin disease (χ 2(2) = 15.52, p = 0.00043), global disease (χ 2(2) = 8.14, p = 0.017) and muscle disease (CMAS χ 2(2) = 17.02, p = 0.0002 and MMT χ 2(2) = 10.56, p = 0.005) in infliximab patients. For patients who switched from infliximab to adalimumab, there was improvement in global disease activity (χ 2(2) = 6.73, p = 0.03), and trends towards improvement in CMAS, MMT8 and modified DAS. The median initial prednisolone dose was 6 [0–10] mg, and final was 2.5 [0–7.5] mg (p
Published: 2020
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8. Juvenile idiopathic inflammatory myositis: an update on pathophysiology and clinical care

Author: Charalampia Papadopoulou, Christine Chew, Meredyth G. Ll. Wilkinson, Liza McCann, and Lucy R. Wedderburn
Subjects: Rheumatology
Published: 2023

9. Similarities and Differences Between Juvenile and Adult Spondyloarthropathies

Author: Corinne Fisher, Coziana Ciurtin, Maria Leandro, Debajit Sen, and Lucy R. Wedderburn
Subjects: juvenile spondyloarthropathy, enthesitis related arthritis, adolescence, enthesitis, adult spondyloarthropathy, Medicine (General), R5-920
Abstract: Spondyloarthritis (SpA) encompasses a broad spectrum of conditions occurring from childhood to middle age. Key features of SpA include axial and peripheral arthritis, enthesitis, extra-articular manifestations, and a strong association with HLA-B27. These features are common across the ages but there are important differences between juvenile and adult onset disease. Juvenile SpA predominantly affects the peripheral joints and the incidence of axial arthritis increases with age. Enthesitis is important in early disease. This review article highlights the similarities and differences between juvenile and adult SpA including classification, pathogenesis, clinical features, imaging, therapeutic strategies, and disease outcomes. In addition, the impact of the biological transition from childhood to adulthood is explored including the importance of musculoskeletal and immunological maturation. We discuss how the changes associated with adolescence may be important in explaining age-related differences in the clinical phenotype between juvenile and adult SpA and their implications for the treatment of juvenile SpA.
Published: 2021
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10. Being on the juvenile dermatomyositis rollercoaster: a qualitative study

Author: Polly Livermore, Suzanne Gray, Kathleen Mulligan, Jennifer N. Stinson, Lucy R. Wedderburn, and Faith Gibson
Subjects: Juvenile dermatomyositis, Qualitative research, Phenomenology, Uncertainty, Psychosocial needs, Pediatrics, RJ1-570, Diseases of the musculoskeletal system, RC925-935
Abstract: Abstract Background Juvenile Dermatomyositis is a rare, potentially life-threatening condition with no known cure. There is no published literature capturing how children and young people feel about their condition, from their perspective. This study was therefore unique in that it asked children and young people what is it like to live with Juvenile Dermatomyositis. Methods Data were obtained from fifteen young people with Juvenile Dermatomyositis, between eight and nineteen years of age from one Paediatric Rheumatology department using audio-recorded interpretive phenomenology interviews. Data were analyzed phenomenologically, using a process that derives narratives from transcripts resulting in a collective composite of participants shared experiences, called a ‘phenomenon’. Results The overarching metaphor of a rollercoaster captures the phenomenon of living with Juvenile Dermatomyositis as a young person, with the ups and downs at different time points clearly described by those interviewed. The five themes plotted on the rollercoaster, began with confusion; followed by feeling different, being sick, steroidal and scared from the medications; uncertainty; and then ended with acceptance of the disease over time. Conclusion Young people were able to talk about their experiences about having Juvenile Dermatomyositis. Our findings will aid clinicians in their practice by gaining a deeper understanding of what daily life is like and highlighting ways to enhance psychosocial functioning. Hopefully, this study and any further resulting studies, will raise understanding of Juvenile Dermatomyositis worldwide and will encourage health care professionals to better assess psychosocial needs in the future.
Published: 2019
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11. Development of a benchmarking toolkit for adolescent and young adult rheumatology services (BeTAR)

Author: Ran A. Cai, Hema Chaplin, Polly Livermore, Martin Lee, Debajit Sen, Lucy R. Wedderburn, Nick Wilkinson, Rachel Jeffery, Andrea Kempa, Imogen Norton, Rachel Tattersall, Yiannis Ioannou, and Despina Eleftheriou
Subjects: Adolescent rheumatology, Standards of care, Benchmarking, Quality improvement, Healthcare services, Patient involvement, Pediatrics, RJ1-570, Diseases of the musculoskeletal system, RC925-935
Abstract: Abstract Background Young people (YP; 12–24 years old) with rheumatic diseases face many challenges associated with chronic illness in addition to the physiological and psychosocial changes of adolescence. Timely access to developmentally appropriate multidisciplinary care is key to successfully managing rheumatic diseases, but gaps in the care of this vulnerable age group still exist. This study aimed to develop a benchmarking toolkit to enable comparative evaluation of YP rheumatology services in order to promote best practice and reduce variations in service delivery. Methods A staged and consultative method was used across a broad group of stakeholders in the UK (YP, parents/other carers, and healthcare professionals, HCPs) to develop this toolkit, with reference to pre-existing standards of YP-friendly healthcare. Eighty-seven YP (median age 19 years, range 12–24 years) and 26 rheumatology HCPs with 1–34 years of experience caring for YP have participated. Results Thirty quality criteria were identified, which were grouped into four main domains: assessment and treatment, information and involvement, accessibility and environment, and continuity of care. Two toolkit versions, one to be completed by HCPs and one to be completed by patients, were developed. These were further refined by relevant groups and face validity was confirmed. Conclusions A toolkit has been developed to systematically evaluate and benchmark YP rheumatology services, which is key in setting standards of care, identifying targets for improvement and facilitating research. Engagement from YP, clinical teams, and commissioners with this tool should facilitate investigation of variability in levels of care and drive quality improvement.
Published: 2019
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12. Biomarkers of Response to Biologic Therapy in Juvenile Idiopathic Arthritis

Author: Varvara Choida, Margaret Hall-Craggs, Bethany R. Jebson, Corinne Fisher, Maria Leandro, Lucy R. Wedderburn, and Coziana Ciurtin
Subjects: juvenile idiopathic arthritis, serological biomarkers, imaging biomarkers, cellular biomarkers, biologics, Therapeutics. Pharmacology, RM1-950
Abstract: Background: Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory arthritis of childhood, characterized by various clinical phenotypes associated with variable prognosis. Significant progress has been achieved with the use of biologic treatments, which specifically block pro-inflammatory molecules involved in the disease pathogenesis. The most commonly used biologics in JIA are monoclonal antibodies and recombinant proteins targeting interleukins 1 (IL-1) and 6 (IL-6), and tumor necrosis factor α (TNF-α). Several biomarkers have been investigated in JIA.Aims: To assess the level of evidence available regarding the role of biomarkers in JIA related to guiding clinical and therapeutic decisions, providing disease prognostic information, facilitating disease activity monitoring and assessing biologic treatment response in JIA, as well as propose new strategies for biologic therapy-related biomarker use in JIA.Methods: We searched PubMed for relevant literature using predefined key words corresponding to several categories of biomarkers to assess their role in predicting and assessing biologic treatment response and clinical remission in JIA.Results: We reviewed serological, cellular, genetic, transcriptomic and imaging biomarkers, to identify candidates that are both well-established and widely used, as well as newly investigated in JIA on biologic therapy. We evaluated their role in management of JIA as well as identified the unmet needs for new biomarker discovery and better clinical applications.Conclusion: Although there are no ideal biomarkers in JIA, we identified serological biomarkers with potential clinical utility. We propose strategies of combining biomarkers of response to biologics in JIA, as well as routine implementation of clinically acceptable imaging biomarkers for improved disease assessment performance.
Published: 2021
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13. Role of CD14+ monocyte-derived oxidised mitochondrial DNA in the inflammatory interferon type 1 signature in juvenile dermatomyositis

Author: Meredyth G Ll Wilkinson, Dale Moulding, Thomas C R McDonnell, Michael Orford, Chris Wincup, Joanna Y J Ting, Georg W Otto, Restuadi Restuadi, Daniel Kelberman, Charalampia Papadopoulou, Sergi Castellano, Simon Eaton, Claire T Deakin, Elizabeth C Rosser, and Lucy R Wedderburn
Subjects: Rheumatology, Immunology, Immunology and Allergy, General Biochemistry, Genetics and Molecular Biology
Abstract: ObjectivesTo define the host mechanisms contributing to the pathological interferon (IFN) type 1 signature in Juvenile dermatomyositis (JDM).MethodsRNA-sequencing was performed on CD4+, CD8+, CD14+and CD19+cells sorted from pretreatment and on-treatment JDM (pretreatment n=10, on-treatment n=11) and age/sex-matched child healthy-control (CHC n=4) peripheral blood mononuclear cell (PBMC). Mitochondrial morphology and superoxide were assessed by fluorescence microscopy, cellular metabolism by13C glucose uptake assays, and oxidised mitochondrial DNA (oxmtDNA) content by dot-blot. Healthy-control PBMC and JDM pretreatment PBMC were cultured with IFN-α, oxmtDNA, cGAS-inhibitor, TLR-9 antagonist and/orn-acetyl cysteine (NAC). IFN-stimulated gene (ISGs) expression was measured by qPCR. Total numbers of patient and controls for functional experiments, JDM n=82, total CHC n=35.ResultsDysregulated mitochondrial-associated gene expression correlated with increased ISG expression in JDM CD14+ monocytes. Altered mitochondrial-associated gene expression was paralleled by altered mitochondrial biology, including ‘megamitochondria’, cellular metabolism and a decrease in gene expression of superoxide dismutase (SOD)1. This was associated with enhanced production of oxidised mitochondrial (oxmt)DNA. OxmtDNA induced ISG expression in healthy PBMC, which was blocked by targeting oxidative stress and intracellular nucleic acid sensing pathways. Complementary experiments showed that, under in vitro experimental conditions, targeting these pathways via the antioxidant drug NAC, TLR9 antagonist and to a lesser extent cGAS-inhibitor, suppressed ISG expression in pretreatment JDM PBMC.ConclusionsThese results describe a novel pathway where altered mitochondrial biology in JDM CD14+ monocytes lead to oxmtDNA production and stimulates ISG expression. Targeting this pathway has therapeutical potential in JDM and other IFN type 1-driven autoimmune diseases.
Published: 2022

14. Clinical signs and symptoms in a joint model of four disease activity parameters in juvenile dermatomyositis: a prospective, longitudinal, multicenter cohort study

Author: E. H. Pieter van Dijkhuizen, Maria De Iorio, Lucy R. Wedderburn, Claire T. Deakin, and on behalf of the JDRG
Subjects: Juvenile dermatomyositis, Disease activity, Bayesian model, Longitudinal data, Clinical associations, Diseases of the musculoskeletal system, RC925-935
Abstract: Abstract Background It is currently impossible to predict the prognosis of patients with juvenile dermatomyositis (JDM). The aim of this study was to find clinical features most strongly associated with outcome variables in JDM as a first step towards tailor-made treatment. Methods In a large, prospectively followed, multicenter cohort study of 340 patients with JDM, each contributing multiple visits, a Bayesian model of disease activity was developed, using the four continuous outcome variables creatine kinase (CK), childhood myositis assessment score (CMAS), manual muscle testing of 8 muscle groups (MMT8) and the physician’s global assessment of disease activity (PGA). Covariates were clinical signs and symptoms. Correlations among visits of the same patient were resolved by introducing subject-specific random effects. Results Myalgia and dysphonia were associated with worse disease activity according to all outcome variables. Periorbital rash, rash on the trunk, rash over large joints, nail fold changes and facial swelling were associated with higher PGA. Notably, periorbital rash was also associated with higher CK and lower CMAS and nail fold changes with lower CMAS. Contractures were associated with lower CMAS and MMT8 and higher PGA. Patients with higher CMAS exhibited a higher MMT8 as well. PGA had the highest probability among the four outcome variables of being abnormal even if the other three outcome variables were normal. Conclusions The signs and symptoms associated with disease activity could be used to stratify patients and adapt treatment plans to disease activity. The correlation between CMAS and MMT8 and the unique information captured by PGA implied that PGA should be maintained as an outcome variable, whereas CMAS and MMT8 might be simplified.
Published: 2018
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15. The transcription factor CREM drives an inflammatory phenotype of T cells in oligoarticular juvenile idiopathic arthritis

Author: Kim Ohl, Helge Nickel, Halima Moncrieffe, Patricia Klemm, Anja Scheufen, Dirk Föll, Viktor Wixler, Angela Schippers, Norbert Wagner, Lucy R. Wedderburn, and Klaus Tenbrock
Subjects: CREM, JIA, Effector T cells, Pediatrics, RJ1-570, Diseases of the musculoskeletal system, RC925-935
Abstract: Abstract Background Inflammatory effector T cells trigger inflammation despite increased numbers of Treg cells in the synovial joint of patients suffering from juvenile idiopathic arthritis (JIA). The cAMP response element (CREM)α is known to play a major role in regulation of T cells in SLE, colitis, and EAE. However, its role in regulation of effector T cells within the inflammatory joint is unknown. Methods CREM expression was analyzed in synovial fluid cells from oligoarticular JIA patients by flow cytometry. Peripheral blood mononuclear cells were incubated with synovial fluid and analyzed in the presence and absence of CREM using siRNA experiments for T cell phenotypes. To validate the role of CREM in vivo, ovalbumin-induced T cell dependent arthritis experiments were performed. Results CREM is highly expressed in synovial fluid T cells and its expression can be induced by treating healthy control PBMCs with synovial fluid. Specifically, CREM is more abundant in CD161+ subsets, than CD161− subsets, of T cells and contributes to cytokine expression by these cells. Finally, development of ovalbumin-induced experimental arthritis is ameliorated in mice with adoptively transferred CREM−/− T cells. Conclusion In conclusion, our study reveals that beyond its role in SLE T cells CREM also drives an inflammatory phenotype of T cells in JIA.
Published: 2018
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16. Allogeneic hematopoietic stem cell transplantation for severe, refractory juvenile idiopathic arthritis

Author: Juliana M. F. Silva, Fani Ladomenou, Ben Carpenter, Sharat Chandra, Petr Sedlacek, Renata Formankova, Vicky Grandage, Mark Friswell, Andrew J. Cant, Zohreh Nademi, Mary A. Slatter, Andrew R. Gennery, Sophie Hambleton, Terence J. Flood, Giovanna Lucchini, Robert Chiesa, Kanchan Rao, Persis J. Amrolia, Paul Brogan, Lucy R. Wedderburn, Julie M. Glanville, Rachael Hough, Rebecca Marsh, Mario Abinun, and Paul Veys
Subjects: Specialties of internal medicine, RC581-951
Abstract: Abstract: Patients with juvenile idiopathic arthritis (JIA) can experience a severe disease course, with progressive destructive polyarthritis refractory to conventional therapy with disease-modifying antirheumatic drugs including biologics, as well as life-threatening complications including macrophage activation syndrome (MAS). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative immunomodulatory strategy for patients with such refractory disease. We treated 16 patients in 5 transplant centers between 2007 and 2016: 11 children with systemic JIA and 5 with rheumatoid factor–negative polyarticular JIA; all were either refractory to standard therapy, had developed secondary hemophagocytic lymphohistiocytosis/MAS poorly responsive to treatment, or had failed autologous HSCT. All children received reduced toxicity fludarabine-based conditioning regimens and serotherapy with alemtuzumab. Fourteen of 16 patients are alive with a median follow-up of 29 months (range, 2.8-96 months). All patients had hematological recovery. Three patients had grade II-IV acute graft-versus-host disease. The incidence of viral infections after HSCT was high, likely due to the use of alemtuzumab in already heavily immunosuppressed patients. All patients had significant improvement of arthritis, resolution of MAS, and improved quality of life early following allo-HSCT; most importantly, 11 children achieved complete drug-free remission at the last follow-up. Allo-HSCT using alemtuzumab and reduced toxicity conditioning is a promising therapeutic option for patients with JIA refractory to conventional therapy and/or complicated by MAS. Long-term follow-up is required to ascertain whether disease control following HSCT continues indefinitely.
Published: 2018
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17. Proceedings of the 23rd Paediatric Rheumatology European Society Congress: part one

Author: F. De Benedetti, J. Anton, M. Gattorno, H. Lachmann, I. Kone-Paut, S. Ozen, J. Frenkel, A. Simon, A. Zeft, E. Ben-Chetrit, H. M. Hoffman, Y. Joubert, K. Lheritier, A. Speziale, J. Guido, Roberta Caorsi, Federica Penco, Alice Grossi, Antonella Insalaco, Maria Alessio, Giovanni Conti, Federico Marchetti, Alberto Tommasini, Silvana Martino, Romina Gallizzi, Annalisa Salis, Francesca Schena, Francesco Caroli, Alberto Martini, Gianluca Damonte, Isabella Ceccherini, Marco Gattorno, Marie-Louise Frémond, Carolina Uggenti, Lien Van Eyck, Isabelle Melki, Darragh Duffy, Vincent Bondet, Yoann Rose, Bénédicte Neven, Yanick Crow, Mathieu P. Rodero, Yvonne Kusche, Johannes Roth, Katarzyna Barczyk-Kahlert, Giovanna Ferrara, Annalisa Chiocchetti, Silvio Polizzi, Josef Vuch, Diego Vozzi, Anna Mondino, Erica Valencic, Serena Pastore, Andrea Taddio, Flavio Faletra, Umberto Dianzani, Ugo Ramenghi, Qing Zhou, Xiaomin Yu, Erkan Demirkaya, Natalie Deuitch, Deborah Stone, Wanxia Tsai, Amanda Ombrello, Tina Romeo, Elaine F. Remmers, JaeJin Chae, Massimo Gadina, Steven Welch, Seza Ozen, Rezan Topaloglu, Mario Abinun, Daniel L. Kastner, Ivona Aksentijevich, Donatella Vairo, Rosalba Monica Ferraro, Giulia Zani, Jessica Galli, Micaela De Simone, Marco Cattalini, Elisa Fazzi, Silvia Giliani, Ebun Omoyinmi, Ariane Standing, Dorota Rowczenio, Annette Keylock, Sonia Melo Gomes, Fiona Price-Kuehne, Sira Nanthapisal, Claire Murphy, Thomas Cullup, Lucy Jenkins, Kimberly Gilmour, Despina Eleftheriou, Helen Lachmann, Philip Hawkins, Nigel Klein, Paul Brogan, Anita Dhanrajani, Mercedes Chan, Stephanie Pau, Janet Ellsworth, Jaime Guzman, Florence A. Aeschlimann, Marinka Twilt, Simon W. Eng, Shehla Sheikh, Ronald M. Laxer, Diane Hebert, Damien Noone, Christian Pagnoux, Susanne M. Benseler, Rae S. Yeung, Christoph Kessel, Katrin Lippitz, Toni Weinhage, Claas Hinze, Helmut Wittkowski, Dirk Holzinger, Niklas Grün, Dirk Föll, Pieter Van Dijkhuizen, Federica Del Chierico, Clara Malattia, Alessandra Russo, Denise Pires Marafon, Nienke M. ter Haar, Silvia Magni-Manzoni, Sebastiaan J. Vastert, Bruno Dallapiccola, Berent Prakken, Fabrizio De Benedetti, Lorenza Putignani, Berna Eren Fidanci, Kenan Barut, Serap Arıcı, Dogan Simsek, Mustafa Cakan, Ezgi D. Batu, Sezgin Şahin, Ayşenur Kısaarslan, Ebru Yilmaz, Özge Basaran, Ferhat Demir, Kubra Ozturk, Zübeyde Gunduz, Betül Sozeri, Balahan Makay, Nuray Ayaz, Onder Yavascan, Ozlem Aydog, Yelda Bilginer, Zelal Ekinci, Dilek Yıldız, Faysal Gök, Muferret Erguven, Erbil Unsal, Ozgur Kasapcopur, For the FMF Arthritis Vasculitis and Orphan Disease Research in Paediatric Rheumatology (FAVOR), Hafize E. Sönmez, Betül Sözeri, Yonatan Butbul, Seza Özen, Claudia Bracaglia, Giusi Prencipe, Manuela Pardeo, Geneviève Lapeyre, Emiliano Marasco, Walter Ferlin, Robert Nelson, Cristina de Min, N. Ruperto, H. I. Brunner, P. Quartier, T. Constantin, E. Alexeeva, K. Marzan, N. Wulffraat, R. Schneider, S. Padeh, V. Chasnyk, C. Wouters, J. B. Kuemmerle-Deschner, T. Kallinich, B. Lauwerys, E. Haddad, E. Nasonov, M. Trachana, O. Vougiouka, K. Leon, E. Vritzali, A. Martini, D. Lovell, PRINTO/PRCSG, Stefano Volpi, Claudia Pastorino, Francesca Kalli, Alessia Omenetti, Sabrina Chiesa, Arinna Bertoni, Paolo Picco, Gilberto Filaci, Elisabetta Traggiai, Marie-Louise Fremond, Naoki Kitabayashi, Olivero Sacco, Isabelle Meyts, Marie-Anne Morren, Carine Wouters, Eric Legius, Isabelle Callebaut, Christine Bodemer, Frederic Rieux-Laucat, Mathieu Rodero, Nadia Jeremiah, Alexandre Belot, Eric Jeziorski, Didier Bessis, Guilhem Cros, Gillian I. Rice, Bruno Charbit, Anne Hulin, Nihel Khoudour, Consuelo Modesto Caballero, Monique Fabre, Laureline Berteloot, Muriel Le Bourgeois, Philippe Reix, Thierry Walzer, Despina Moshous, Stéphane Blanche, Alain Fischer, Brigitte Bader-Meunier, Frédéric Rieux-Laucat, K. Annink, N. ter Haar, S. Al-Mayouf, G. Amaryan, K. Barron, S. Benseler, P. Brogan, L. Cantarini, M. Cattalini, A. Cochino, F. Dedeoglu, A. De Jesus, O. Dellacasa, E. Demirkaya, P. Dolezalova, K. Durrant, G. Fabio, R. Gallizzi, R. Goldbach-Mansky, E. Hachulla, V. Hentgen, T. Herlin, M. Hofer, H. Hoffman, A. Insalaco, A. Jansson, I. Koné-Paut, A. Kozlova, J. Kuemmerle-Deschner, R. Laxer, S. Nielsen, I. Nikishina, A. Ombrello, E. Papadopoulou-Alataki, A. Ravelli, D. Rigante, R. Russo, Y. Uziel, Nienke ter Haar, Jerold Jeyaratnam, Anna Simon, Matteo Doglio, Jordi Anton, Consuelo Modesto, Pierre Quartier, Esther Hoppenreijs, Luca Cantarini, Loredana Lepore, Inmaculada Calvo Penades, Christina Boros, Rita Consolini, Donato Rigante, Ricardo Russo, Jana Pachlopnik Schmid, Thirusha Lane, Nicolino Ruperto, Joost Frenkel, Chiara Passarelli, Elisa Pisaneschi, Virginia Messia, Antonio Novelli, Fabrizio Debenedetti, P. A. Brogan, X. Wei, Martina Finetti, Francesca Orlando, Elisabetta Cortis, Angela Miniaci, Nicola Ruperto, Charlotte Eijkelboom, Pavla Dolezalova, Isabelle Koné-Paut, Marija Jelusic-Drazic, Liliana Bezrodnik, Mari Carmen Pinedo, Valda Stanevicha, Marielle van Gijn, Silvia Federici, Hermann Girschick, Gerd Ganser, Susan Nielsen, Troels Herlin, Sulaiman Mohammed Al-Mayouf, Michael Hofer, Jasmin Kuemmerle-Deschner, Susanne Schalm, Annette Jansson, on behalf of PRINTO and Eurofever registry, Marta Marchi, Chiara Marini, Angelo Ravelli, Alberto Garaventa, Sonia Carta, Enrica Balza, Patrizia Castellani, Caterina Pellecchia, Silvia Borghini, Maria Libera Trotta, Anna Rubartelli, Andrew Henrey, Thomas Loughin, Roberta Berard, Natalie Shiff, Roman Jurencak, Susanne Benseler, Lori Tucker, on behalf of ReACCh-Out Investigators, Charalampia Papadopoulou, Ying Hong, Petra Krol, Yiannis Ioannou, Clarissa Pilkington, Hema Chaplin, Stephania Simou, Marietta Charakida, Lucy Wedderburn, Lynn R. Spiegel, Sara Ahola Kohut, Jennifer Stinson, Paula Forgeron, Miriam Kaufman, Nadia Luca, Khush Amaria, Mary Bell, J Swart, F. Boris, E. Castagnola, A. Groll, G. Giancane, G. Horneff, H. I. Huppertz, T. Wolfs, E. Alekseeva, V. Panaviene, F. Uettwiller, V. Stanevicha, L. M. Ailioaie, E. Tsitami, S. Kamphuis, G. Susic, F. Sztajnbok, B. Flato, A. Pistorio, Stephanie J. W. Shoop, Suzanne M. M. Verstappen, Janet E. McDonagh, Wendy Thomson, Kimme L. Hyrich, CAPS, Maarit Tarkiainen, Pirjo Tynjala, Pekka Lahdenne, Janne Martikainen, Acute-JIA Study Group, Meredyth Wilkinson, Christopher Piper, Georg Otto, Claire T. Deakin, Stefanie Dowle, Stefania Simou, Daniel Kelberman, Claudia Mauri, Elizabeth Jury, David Isenberg, Lucy R. Wedderburn, Kiran Nistala, I. Foeldvari, D. J. Lovell, G. Simonini, M. Bereswill, J. Kalabic, Kiem Oen, Brian M. Feldman, Brenden Dufault, Jennifer Lee, Karen Watanabe Duffy, Ciaran Duffy, ReACCh-Out Investigators, N. Tzaribachev, G. Vega-Cornejo, I. Louw, A. Berman, I. Calvo, R. Cuttica, F. Avila-Zapata, R. Cimaz, E. Solau-Gervais, R. Joos, G. Espada, X. Li, M. Nys, R. Wong, S. Banerjee, For Pediatric Rheumatology International Trials Organization (PRINTO)/Pediatric Rheumatology Collaborative Study Group (PRCSG), Rebecca Nicolai, Margherita Verardo, Adele D’Amico, Luisa Bracci-Laudiero, Gian Marco Moneta, Gillian Rice, Anne-Laure Mathieu, Sulliman O. Omarjee, Tracy A. Briggs, James O’Sullivan, Simon Williams, Rolando Cimaz, Eve Smith, Michael W. Beresford, Yanick J. Crow, GENIAL Investigators, UK JSLE Study Group, Madeleine Rooney, Nick Bishop, joyce davidson, Clarissa pilkington, Michael Beresford, Jacqui Clinch, Rangaraj Satyapal, Helen Foster, Janet Gardner Medwin, Janet McDonagh, Sue Wyatt, On Behalf of the British Society for Paediatric and Adolescent Rheumatology, Valentina Litta Modignani, Francesco Baldo, Stefano Lanni, Alessandro Consolaro, Giovanni Filocamo, Helen J. Lachmann, on behalf of Eurofever Registry, Gianmarco Moneta, Camilla Celani, Bilade Cherqaoui, Linda Rossi-Semerano, Perrine Dusser, Véronique Hentgen, Claire Grimwood, Linda Rossi, Isabelle Kone Paut, Veronique Hentgen, Denise Lasigliè, Denise Ferrera, Giulia Amico, Marco Di Duca, Laura Obici, Roberto Ravazzolo, Ryuta Nishikomori, Juan Arostegui, Andrea Petretto, Chiara Lavarello, Elvira Inglese, Federica Vanoni, Michaël Hofer, on behalf of EUROFEVER PROJECT, P. N. Hawkins, T. van der Poll, U. A. Walker, H. H. Tilson, Pascal N. Tyrrell, Raphaela Goldbach-Mansky, Norbert Blank, Hal M. Hoffman, Elisabeth Weissbarth-Riedel, Boris Huegle, Tilmann Kallinich, Ahmet Gul, Marlen Oswald, Fatma Dedeoglu, Aki Hanaya, Takako Miyamae, Manabu Kawamoto, Yumi Tani, Takuma Hara, Yasushi Kawaguchi, Satoru Nagata, Hisashi Yamanaka, Almira Ćosićkić, Fahrija Skokić, Belkisa Čolić, Sanimir Suljendić, Anna Kozlova, Irina Mersiyanova, Mariya Panina, Lily Hachtryan, Vasiliy Burlakov, Elena Raikina, Alexey Maschan, Anna Shcherbina, Banu Acar, Meryem Albayrak, Betul Sozeri, Sezgin Sahin, Amra Adrovic, Nese Inan, Serhan Sevgi, Caroline M. Andreasen, Anne Grethe Jurik, Mia B. Glerup, Christian Høst, Birgitte T. Mahler, Ellen-Margrethe Hauge, Cecilia Lazea, Laura Damian, Calin Lazar, Rodica Manasia, Chloe M. Stephenson, Vimal Prajapati, Paivi M. Miettunen, Dilek Yılmaz, Yavuz Tokgöz, Yasin Bulut, Harun Çakmak, Ferah Sönmez, Elif Comak, Gülşah Kaya Aksoy, Mustafa Koyun, Sema Akman, Yunus Arıkan, Ender Terzioğlu, Osman Nidai Özdeş, İbrahim Keser, Hüseyin Koçak, Ayşen Bingöl, Aygen Yılmaz, Reha Artan, X. Xu, Fatemeh F. Mehregan, Vahid Ziaee, Mohammad H. Moradinejad, Francesco La Torre, Clotilde Alizzi, Pio D’Adamo, G. Junge, J. Gregson, Hasmik Sargsyan, Hulya Zengin, Berna E. Fidanci, Cagla Kaymakamgil, Dilek Konukbay, Dilek Yildiz, Faysal Gok, Iris Stoler, Judith Freytag, Banu Orak, Christine Seib, Lars Esmann, Eva Seipelt, Faekah Gohar, Dirk Foell, Ismail Dursun, Sebahat Tulpar, Sibel Yel, Demet Kartal, Murat Borlu, Funda Bastug, Hakan Poyrazoglu, Zubeyde Gunduz, Kader Kose, Mehmet E. Yuksel, Abdullah Calıskan, Ahmet B. Cekgeloglu, Ruhan Dusunsel, Katerina Bouchalova, Jana Franova, Marcel Schuller, Marie Macku, Katerina Theodoropoulou, Raffaella Carlomagno, Annette von Scheven-Gête, Claudia Poloni, Laura O. Damian, Dan Cosma, Amanda Radulescu, Dan Vasilescu, Liliana Rogojan, Simona Rednic, Mihaela Lupse, Lien De Somer, Pierre Moens, Rocio Galindo Zavala, Laura Martín Pedraz, Esmeralda Núñez Cuadros, Gisela Díaz-Cordovés Rego, Antonio L. Urda Cardona, Ilaria Dal Forno, Sara Pieropan, Ombretta Viapiana, Davide Gatti, Gloria Dallagiacoma, Paola Caramaschi, Domenico Biasi, Daniel Windschall, Ralf Trauzeddel, Hartwig Lehmann, Rainer Berendes, Maria Haller, Manuela Krumrey-Langkammerer, Antje Nimtz-Talaska, Philipp Schoof, Ralf Felix Trauzeddel, Christine Nirschl, Estefania Quesada-Masachs, Carla Aguilar Blancafort, Sara Marsal Barril, Francisca Aguiar, Rita Fonseca, Duarte Alves, Ana Vieira, Alberto Vieira, Jorge A. Dias, Iva Brito, Gordana Susic, Vera Milic, Goran Radunovic, Ivan Boricic, Pauline Marteau, Catherine Adamsbaum, Michel De Bandt, Irène Lemelle, Chantal Deslandre, Tu Anh Tran, Anne Lohse, Elisabeth Solau-Gervais, Pascal Pillet, Julien Wipff, Cécile Gaujoux-Viala, Sylvain Breton, Valérie Devauchelle-Pensec, Sandra Gran, Olesja Fehler, Stefanie Zenker, Michael Schäfers, Thomas Vogl, Severine Guillaume Czitrom, EH Pieter Van Dijkhuizen, Silvia Magni Manzoni, Francesca Magnaguagno, Laura Tanturri de Horatio, Nienke M. Ter Haar, Annemieke S. Littooij, Vitor A. Teixeira, Raquel Campanilho-Marques, Ana F. Mourão, Filipa O. Ramos, Manuela Costa, Wafa A. Madan, Orla G. Killeen, Adriana Rodriguez Vidal, Diana Sueiro Delgado, Maria Isabel Gonzalez Fernandez, Berta Lopez Montesinos, Aleksey Kozhevnikov, Nina Pozdeeva, Mikhail Konev, Evgeniy Melchenko, Vladimir Kenis, Gennadiy Novik, Aysenur Pac Kısaarslan, Butsabong Lerkvaleekul, Suphaneewan Jaovisidha, Witaya Sungkarat, Niyata Chitrapazt, Praman Fuangfa, Thumanoon Ruangchaijatuporn, Soamarat Vilaiyuk, Dan Ø. Pradsgaard, Arne Hørlyck, Anne H. Spannow, Carsten W. Heuck, Talia Diaz, Fernando Garcia, Lorenia De La Cruz, Nadina Rubio, Joanna Świdrowska-Jaros, Elzbieta Smolewska, Mirta Lamot, Lovro Lamot, Mandica Vidovic, Edi Paleka Bosak, Ivana Rados, Miroslav Harjacek, Nikolay Tzaribachev, Polymnia Louka, Romiesa Hagoug, Chiara Trentin, Olga Kubassova, Mark Hinton, Mikael Boesen, Olena A. Oshlianska, Illya A. Chaikovsky, G. Mjasnikov, A. Kazmirchyk, Umberto Garagiola, Irene Borzani, Paolo Cressoni, Fabrizia Corona, Eszter Dzsida, Giampietro Farronato, Antonella Petaccia, Alenka Gagro, Agneza Marija Pasini, Goran Roic, Ozren Vrdoljak, Lucija Lujic, Matija Zutelija-Fattorini, Monika M. Esser, Deepthi R. Abraham, Craig Kinnear, Glenda Durrheim, Mike Urban, Eileen Hoal, Victoria B. Nikolayenko, Kubilay Şahin, Yasar Karaaslan, Adele Civino, Giovanni Alighieri, Sergio Davì, Roberto Rondelli, Andrea Magnolato, Francesca Ricci, Alma Olivieri, Valeria Gerloni, Bianca Lattanzi, Francesca Soscia, Alessandro De Fanti, Stefania Citiso, Lorenzo Quartulli, Maria Cristina Maggio, Manuela Marsili, Maria Antonietta Pelagatti, Valentino Conter, Franca Fagioli, Andrea Pession, Marco Garrone, Mariangela Rinaldi, Jaime De Inocencio, Stella Garay, Daniel J. Lovell, Berit Flato, EPOCA Study Group, Angela Aquilani, Simona Cascioli, Ivan Caiello, Denise Pires-Marafón, Rita Carsetti, Emily Robinson, Salvatore Albani, Wilco de Jager, Sytze de Roock, Trang Duong, Justine Ellis, Kimme Hyrich, Laetitia Jervis, Daniel Lovell, Lucy Marshall, Elizabeth D. Mellins, Kirsten Minden, Jane Munro, Peter A. Nigrovic, Jason Palman, Sunil Sampath, Laura E. Schanberg, Susan D. Thompson, Richard Vesely, Chris Wallace, Chris Williams, Qiong Wu, Nico Wulffraat, Rae S. M. Yeung, M. B. Seyger, D. Arikan, J. K. Anderson, A. Lazar, D. A. Williams, C. Wang, R. Tarzynski-Potempa, J. S. Hymans, Gabriele Simonini, Erika Scoccimarro, Irene Pontikaki, Teresa Giani, Alessandro Ventura, Pier Luigi Meroni, Gaetana Minnone, Marzia Soligo, Luigi Manni, Luisa Bracci Laudiero, Noortje Groot, I. Grein, N. M. Wulffraat, R. Schepp, G. Berbers, C. C. Barbosa Sandoval de Souza, V. Paes Leme Ferriani, G. Pileggi, S. de Roock, Ingrid H. R. Grein, Silvia Scala, Elisa Patrone, Casper Schoemaker, on behalf of Dutch JIA patient organization, Wendy Costello, on behalf of ENCA, Suzanne Parsons, Jean-David Cohen, Damien Bentayou, Marc-Antoine Bernard Brunel, Sonia Trope, Jens Klotsche, Miriam Listing, Martina Niewerth, Gerd Horneff, Angelika Thon, Hans-Iko Huppertz, Kirsten Mönkemöller, Ivan Foeldvari, ICON study group, Achille Marino, Stefano Stagi, Niccolò Carli, Federico Bertini, Adriana S. Díaz-Maldonado, Sally Pino, Pilar Guarnizo, Alfonso Ragnar Torres-Jimenez, Berenice Sanchez-Jara, Eunice Solis-Vallejo, Adriana Ivonne Cespedes-Cruz, Maritza Zeferino-Cruz, Julia Veronica Ramirez-Miramontes, Ankur Kumar, Anju Gupta, Deepti Suri, Amit Rawat, Nandita Kakkar, Surjit Singh, Özge A. Gücenmez, Erbil Ünsal, Bo Magnusson, Karina Mördrup, Anna Vermé, Christina Peterson, Board of the Swedish Pediatric Rheumatology Registry, Caroline Freychet, Jean Louis Stephan, Cathryn E. Harkness, Leanne Foster, Emma Henry, Pauline Taggart, Coskun F. Ozkececi, Esra Kurt, Gokalp Basbozkurt, Daiva Gorczyca, Jacek Postępski, Aleksandra Czajkowska, Bogumiła Szponar, Mariola Paściak, Anna Gruenpeter, Iwona Lachór-Motyka, Daria Augustyniak, Edyta Olesińska, Emediong S. Asuka, Tatyana Golovko, Samuel U. Aliejim, Emilio Inarejos Clemente, Estibaliz Iglesias Jimenez, Joan Calzada Hernandez, Sergi Borlan Fernandez, Clara Gimenez Roca, David Moreno Romo, Natalia Rodriguez Nieva, Juan Manuel Mosquera Angarita, Jordi Anton Lopez, Esmeralda Nuñez-Cuadros, Gisela Diaz-Cordovés, Rocío Galindo-Zavala, Antonio Urda-Cardona, Antonio Fernández-Nebro, Daniel Álvarez de la Sierra, Marina Garcia Prat, Mónica Martínez Gallo, Ricardo Pujol Borrell, Ana M. Marín Sánchez, Etienne Merlin, Sylvie Fraitag, Jean-Louis Stephan, Federico Annoni, Giancarla Di Landro, Sofia Torreggiani, Marta Torcoletti, Georgina Tiller, Jo Buckle, Angela Cox, Peter Gowdie, Roger C. Allen, Jonathan D. Akikusa, Hayde G. Hernández-Huirache, Edel R. Rodea-Montero, William Fahy, Christelle Sordet, Karin B. Berggren, Johanna T. Kembe, Joyce Bos, Wineke Armbrust, Marco van Brussel, Jeanette Cappon, Pieter Dijkstra, Jan Geertzen, Elizabeth Legger, Marion van Rossum, Pieter Sauer, Otto Lelieveld, Levent Buluc, Gur Akansel, Bahar Muezzinoglu, Ljubov Rychkova, Tatyana Knyazeva, Anna Pogodina, Tatyana Belova, Tamara Mandzyak, Ekaterina Kulesh, Alessandro Cafarotti, Cosimo Giannini, Roberta Salvatore, Giuseppe Lapergola, Caterina Di Battista, Maria Loredana Marcovecchio, Raffaella Basilico, Piernicola Pelliccia, Francesco Chiarelli, Luciana Breda, Beverley Almeida, Sarah Tansley, Harsha Gunawardena, Neil McHugh, Juvenile Dermatomyositis Research Group (JDRG), Jessie Aouizerate, Marie De Antonio, Christine Barnerias, Guillaume Bassez, Isabelle Desguerre, Romain Gherardi, Jean-Luc Charuel, François-Jérôme Authier, Cyril Gitiaux, C. H. Spencer, Rabheh Abdul Aziz, Chack-Yung Yu, Brent Adler, Sharon Bout-Tabaku, Katherine Lintner, Melissa Moore-Clingenpeel, Liza McCann, Nicola Ambrose, Mario Cortina-Borja, Juvenile Dermatomyositis Cohort and Biomarker Study (JCDBS), Prasad T. Oommen, Fabian Speth, Johannes-Peter Haas, Working Group “Juvenile Dermatomyositis” of the German Society for Paediatric and Adolescent Rheumatology (GKJR), Claudio Lavarello, Gabriella Giancane, Angela Pistorio, Lisa Rider, Rohit Aggarwal, Sheila K. Oliveira, Ruben Cuttica, Michel Fischbach, Gary Sterba, Karine Brochard, Frank Dressler, Patrizia Barone, Ruben Burgos-Vargas, Elizabeth Candell Chalom, Marine Desjonqueres, Graciela Espada, Anders Fasth, Stella Maris Garay, Rose-Marie Herbigneaux, Claire Hoyoux, Chantal Job Deslandre, Frederick W. Miller, Jiri Vencovsky, Erdal Sag, Gulsev Kale, Haluk Topaloglu, Beril Talim, Francesco Zulian, Tadej Avcin, Roberto Marini, Anne Pagnier, Michel Rodiere, Christine Soler, Rebecca Ten Cate, Yosef Uziel, Jelena Vojinovic, Ana V. Villarreal, Nydia Acevedo, Yuridiana Ramirez, Enrique Faugier, Rocio Maldonado, Bita Arabshahi, John H. Lee, Ian Leibowitz, Lawrence O. Okong’o, Jo Wilmshurst, Monika Esser, Christiaan Scott, Ezgi Deniz Batu, Nagehan Emiroglu, Hafize Emine Sonmez, Gokcen Dilsa Tugcu, Zehra Serap Arici, Ebru Yalcin, Deniz Dogru, Ugur Ozcelik, Mithat Haliloglu, Nural Kiper, Masato Yashiro, Mutsuko Yamada, Toshihiko Yabuuchi, Tomonobu Kikkawa, Nobuyuki Nosaka, Yosuke Fujii, Yukie Saito, Hirokazu Tsukahara, Sulaiman M. Al-Mayouf, Nora AlMutiari, Mohammed Muzaffer, Rawiah shehata, Adel Al-Wahadneh, Reem Abdwani, Safia Al-Abrawi, Mohammed Abu-shukair, Zeyad El-Habahbeh, Abdullah Alsonbul, Aleksandra Szabat, Monika Chęć, Violetta Opoka-Winiarska, Biman Saikia, Ranjana W. Minz, Christine Arango, Clara Malagon, Maria D. P. Gomez, Angela C. Mosquera, Ricardo Yepez, Tatiana Gonzalez, Camilo Vargas, GRIP study group, Marta Balzarin, Biagio Castaldi, Elena Reffo, Francesca Sperotto, Giorgia Martini, Alessandra Meneghel, Ornella Milanesi, Ozgur Kasapçopur, Maria Teresa Terreri, Ekaterina Alexeeva, Maria Katsicas, Mikhail Kostik, Thomas Lehman, W.-Alberto Sifuentes-Giraldo, Vanessa Smith, Flavio Sztajnbok, Tadey Avcin, Maria Jose Santos, Dana Nemcova, Cristina Battagliotti, Liora Harel, Mahesh Janarthanan, Kathryn Torok, Nicola Helmus, Eileen Baildem, Michael Blakley, Kim Fligelstone, Antonia Kienast, Clare Pain, Amanda Saracino, Gabriele Simoni, Lisa Weibel, Maria K. Osminina, Nathalia A. Geppe, Olga V. Niconorova, Olesya V. Karashtina, Oksana V. Abbyasova, Olga V. Shpitonkova, Sinem Durmus, Hafize Uzun, Angela Mauro, Eleonora Fanti, Fabio Voller, Franca Rusconi, Fernando Garcia-Rodriguez, Ana V. Villarreal-Treviño, Angel J. Flores-Pineda, Paola B. Lara-Herrea, Diego R. Salinas-Encinas, Talia Diaz-Prieto, Maria R. Maldonado-Velazquez, Sarbelio Moreno-Espinosa, Enrique Faugier-Fuentes, Mirella Crapanzano, Ilaria Parissenti, Man S. Parihar, Pandiarajan Vignesh, ManojKumar Rohit, Kavitha Gopalan, Savita V. Attri, Alan Salama, David Jayne, Mark Little, Yulia Kostina, Galina Lyskina, Olga Shpitonkova, Alena Torbyak, Olga Shirinsky, Maria Francesca Gicchino, Maria Cristina Smaldone, Mario Diplomatico, Alma Nunzia Olivieri, C H. Spencer, Richard McClead, Hiren Patel, Chung-Yung Yu, Dita Cebecauerová, Tomáš Dallos, Edita Kabíčková, Martin Kynčl, Daniela Chroustová, Jozef Hoza, Dana Němcová, Vladimír Tesař, Pavla Doležalová, Tuncay Hazirolan, Fatih Ozaltin, Fabiola Almeida, Isabela H. Faria de Paula, Maíra M. Sampaio, Fernando N. Arita, Andressa G. Alves, Maria Carolina Santos, Eunice M. Okuda, Silvana B. Sacchetti, Fernanda Falcini, Marini Francesca, Gemma Lepri, Marco Matucci-Cerinic, Maria Luisa Brandi, Hakan Kisaoglu, Sema Misir, Selim Demir, Yuksel Aliyazicioglu, Mukaddes Kalyoncu, Carlos Eduardo Ramalho, Fabiola D. Almeida, Joan Calzada-Hernández, Rosa Bou, Estíbaliz Iglesias, Judith Sánchez-Manubens, Fredy Hermógenes Prada Martínez, Clara Giménez Roca, Sergi Borlan Fernández, Marek Bohm, Kamran Mahmood, Valentina Leone, Mark Wood, Ken-Ichi Yamaguchi, Satoshi Fujikawa, Working Group of Behçet’s Disease, Pediatric Rheumatology Association of Japan (PRAJ), Kyu Yeun Kim, Do Young Kim, Dong Soo Kim, Maka Ioseliani, Ivane Chkhaidze, Maia Lekishvili, Nana Tskhakaia, Shorena Tvalabeishvili, Aleksandre Kajrishvili, Maiko Takakura, Masaki Shimizu, Natsumi Inoue, Mao Mizuta, Akihiro Yachie, Giovanni Corsello, Maryam Piram, Carla Maldini, Sandra Biscardi, Nathalie Desuremain, Catherine Orzechowski, Emilie Georget, Delphine Regnard, Isabelle Kone-Paut, Alfred Mahr, Mihaela Sparchez, Zeno Sparchez, Nydia Acevedo Silva, Ana V. Villarreal Treviño, Yuridiana Ramirez Loyola, Talia Diaz Prieto, Enrique Faugier Fuentes, Maria D. R. Maldonado Velazquez, Pilar Perez, Sagar Bhattad, Ranjana Minz, Jitendra Shandilya, Pediatric Allergy and Immunology Unit, PGIMER, Chandigarh, Ana Villarreal, Yuridiana Ramírez, Zeynep Birsin Özçakar, Suat Fitoz, Fatos Yalcinkaya, Annacarin Horne, Francesca Minoia, Francesca Bovis, Sergio Davi, Priyankar Pal, Kimo Stein, Sandra Enciso, Michael Jeng, Despoina Maritsi, Randy C. Cron, Anne Thorwarth, Sae Lim von Stuckrad, Angela Rösen-Wolff, Hella Luksch, Patrick Hundsdoerfer, Peter Krawitz, Nuray Aktay Ayaz, Doğan Simsek, Şebnem Sara Kılıc, Emine Sonmez, Aysenur Pac Kisaarslan, Ozge Altug Gucenmez, Z. Serap Arıcı, Fatih Kelesoglu, Zelal Ekinci Ekinci, Maria Miranda-Garcia, Carolin Pretzer, Michael Frosch, F. Gohar, Angela McArdle, Niamh Callan, Belinda Hernandez, Miha Lavric, Oliver FitzGerald, Stephen R. Pennington, Joachim Peitz, Joern Kekow, Ariane Klein, Anna C. Schulz, Frank Weller-Heinemann, Anton Hospach, J-Peter Haas, BIKER collaborative group, Karen Put, Jessica Vandenhaute, Anneleen Avau, Annemarie van Nieuwenhuijze, Ellen Brisse, Tim Dierckx, Omer Rutgeerts, Josselyn E. Garcia-Perez, Jaan Toelen, Mark Waer, Georges Leclercq, An Goris, Johan Van Weyenbergh, Adrian Liston, Patrick Matthys, Carine H. Wouters, Yasuo Nakagishi, Michael J. Ombrello, Victoria Arthur, Anne Hinks, Patricia Woo, International Childhood Arthritis Genetics (INCHARGE) Consortium, Barbara Stanimirovic, Biljana Djurdjevic-Banjac, Olivera Ljuboja, Boris Hugle, MArgarita Onoufriou, Olga Vougiouka, Kenza Bouayed, Sanae El Hani, Imane Hafid, Nabiha Mikou, Nunu Shelia, Mari Laan, Jaanika Ilisson, and Chris Pruunsild
Subjects: Pediatrics, RJ1-570, Diseases of the musculoskeletal system, RC925-935
Published: 2017
Full Text: View/download PDF

18. Proceedings of the 23rd Paediatric Rheumatology European Society Congress: part three

Author: Riccardo Papa, Alessandro Consolaro, Francesca Minoia, Roberta Caorsi, Gianmichele Magnano, Marco Gattorno, Angelo Ravelli, Paolo Picco, Roberto Pillon, Denise Pires Marafon, Lidia Meli, Claudia Bracaglia, Andrea Taddio, Fabrizio De Benedetti, Enes Turan, Sara Sebnem Kilic, Yasuhiko Itoh, Tomoko Shigemori, Shingo Yamanishi, Hidehiko Nagasaki, Ela Tarakci, Nilay Arman, Devrim Tarakci, Yusuf S. Akgul, Ozgur Kasapcopur, Emily Wilson, Hanna Lythgoe, Eve Smith, Jenny Preston, Michael W. Beresford, Lynn R. Spiegel, Jennifer Stinson, Mark Connelly, Adam Huber, Nadia Luca, Argerie Tsimicalis, Stephanie Luca, Naweed Tajuddin, Roberta Berard, Julie Barsalou, Sarah Campillo, Brian Feldman, Shirley Tse, Paul Dancey, Ciaran Duffy, Nicole Johnson, Patrick McGrath, Natalie Shiff, Lori Tucker, Charles Victor, Chitra Lalloo, Lauren Harris, Joseph Cafazzo, Kristin Houghton, Ronald Laxer, Madeleine Rooney, Roisin Campbell, Catherine Wright, Wineke Armbrust, Otto Lelieveld, Jolanda Tuinstra, Nico Wulffraat, Joyce Bos, Jeanette Cappon, Marion van Rossum, Mariët Hagedoorn, Anna Vermé, Ylva Lampela, Ayse Huri Ozdogan, S. Ugurlu, K. Barut, A. Androvic, O. Kasapçopu, Jody Etheridge, Katie Dobson, Sue Kemp, AnnaCarin Horne, Karin Palmblad, Malin Höglund, Natalia Stepanenko, Svetlana Salugina, Evgeny Fedorov, Irina Nikishina, Maria Kaleda, Kenan Barut, Amra Adrovic, Sezgin Sahin, Laurence Toumoulin, Johnny Frossard, Stephanie Archimbaut, Anne Paitier, Rolande Guastalli, Severine Guillaume Czitrom, Sirirat Charuvanij, Chollada Chaiyadech, Takako Miyamae, Hisashi Yamanaka, Cecile Picard, Guillaume Thouvenin, Caroline Kannengiesser, Jean-Christophe Dubus, Nadia Jeremiah, Frédéric Rieux-Laucat, Bruno Crestani, Véronique Secq, Christelle Ménard, Martine Reynaud-Gaubert, Françoise Thivolet-Bejui, Philippe Reix, Alexandre Belot, Ezgi Deniz Batu, Hafize Emine Sonmez, Abdulsamet Erden, Ekim Z. Taskiran, Omer Karadag, Umut Kalyoncu, İbrahim Oncel, Berkan Kaplan, Zehra Serap Arici, Cagri Mesut Temucin, Haluk Topaloglu, Yelda Bilginer, Mehmet Alikasifoglu, Seza Ozen, Lien Van Eyck, Ellen De Langhe, Isabelle Jéru, Erika Van Nieuwenhove, Vasiliki Lagou, Paul J. Baker, Jocelyn Garcia-Perez, James Dooley, Lien De Somer, Raf Sciot, Pierre-Yves Jeandel, Julia Ruuth-Praz, Bruno Copin, Myrna Medley-Hashim, Andre Megarbane, Sinisa Savic, An Goris, Serge Amselem, Adrian Liston, Seth Masters, Carine Wouters, Nami Okamoto, Yuko Sugita, Kousuke Shabana, Takuji Murata, Hiroshi Tamai, Juliana Ferenczová, Erika Banóova, Pavol Mrážik, Veronika Vargova, Dubravko Bajramovic, Ksenija Stekic Novacki, Kristina Potocki, Marijan Frkovic, Marija Jelusic, Olga Kostareva, Svetlana Arsenyeva, Anna Shapovalenko, Lennart Jans, Nele Herregods, Jacob Jaremko, Rik Joos, Joke Dehoorne, Xenofon Baraliakos, Sofia Ramiro, Julio C. Casasola-Vargas, Désirée van der Heijde, Robert Landewé, Ruben Burgos-Vargas, Shirley M. Tse, Gerd Horneff, Kristina Unnebrink, Jaclyn K. Anderson, Aysenur Paç Kisaarslan, Betül Sözeri, Zübeyde Gündüz, Gökmen Zararsız, Hakan Poyrazoğlu, Ruhan Düşünsel, Kazutaka Ouchi, Shinji Akioka, Hiroshi Kubo, Norio Nakagawa, Hajime Hosoi, Lovro Lamot, Fran Borovecki, Sanja Kapitanovic, Kristina Gotovac, Mandica Vidovic, Mirta Lamot, Edi Paleka Bosak, Miroslav Harjacek, Ricardo A. Russo, María M. Katsicas, Ruben Burgos Vargas, Ana L. Ortiz-Peyegahud, Zhang Pingping, Mou Yikun, Qi Jun, Jiang Yutong, Gu Jieruo, Mikhail M. Kostik, Shilova Ekaterina, Ilia Avrusin, Yuriy Korin, Olga Kopchak, Eugenia Isupova, Irina Chikova, Panova Tatyana, Margarita Dubko, Vera Masalova, Ludmila Snegireva, Tatyana Kornishina, Olga Kalashnikova, Vyacheslav Chasnyk, Tatyana Likhacheva, N. Ruperto, H. I. Brunner, P. Quartier, T. Constantin, E. Alexeeva, R. Schneider, I. Kone-Paut, K. Schikler, K. Marzan, N. Wulffraat, S. Padeh, V. Chasnyk, C. Wouters, J. B. Kuemmerle-Deschner, T. Kallinich, B. Lauwerys, E. Haddad, E. Nasonov, M. Trachana, O. Vougiouka, K. Leon, A. Speziale, K. Lheritier, E. Vritzali, A. Martini, D. Lovell, PRINTO/PRCSG, Nienke Ter Haar, Rianne Scholman, Wilco de Jager, Tamar Tak, Pieter Leliefeld, Bas Vastert, Sytze de Roock, Ariane de Ganck, Nadia Ryter, Miha Lavric, Dirk Foell, Renee F. Modica, Kathleen G. Lomax, Pamela Batzel, Armelle Cassanas, Melissa E. Elder, Rina Denisova, Ekaterina Alexeeva, Saniya Valieva, Tatyana Bzarova, Kseniya Isayeva, Tatyana Sleptsova, Olga Lomakina, Alexandra Chomahidze, Margarita Soloshenko, Meyry Shingarova, Elena Kachshenko, Wilco De Jager, Sebastiaan J. Vastert, Gerdien Mijnheer, Berent J. Prakken, Nico M. Wulffraat, Hafize E. Sönmez, Asuman N. Karhan, Ezgi D. Batu, Zehra S. Arıcı, Ersin Gümüş, Hülya Demir, Aysel Yüce, Seza Özen, Jasmina Ahluwalia, Bhavneet Bharti, Sweta Rajpal, Varun Uppal, Alaknanda Walia, Surjit S. Samlok, Narender Kumar, Clarissa C. Valões, Beatriz C. Molinari, Ana Claudia G. Pitta, Natali W. Gormezano, Sylvia C. Farhat, Kátia Kozu, Adriana M. Sallum, Simone Appenzeller, Ana Paula Sakamoto, Maria T. Terreri, Rosa M. Pereira, Claudia S. Magalhães, Cássia Maria Barbosa, Francisco Hugo Gomes, Eloisa Bonfá, Clovis A. Silva, Kubra Ozturk, Zelal Ekinci, Maie Helal, Natalia Cabrera, Jean Christophe Lega, Jocelyne Drai, Rene Ecochard, O. V. Shpitonkova, N. S. Podchernyaeva, Y. O. Kostina, N. G. Dashkova, M. K. Osminina, Gozde Yucel, Ahmet Arvas, Nandini Moorthy, Paraskevi Dimou, Angela Midgley, Matthew Peak, Simon C. Satchell, Rachael D. Wright, Rachel Corkhill, Eve M. Smith, Sagar Bhattad, Amit Rawat, Surjit Singh, Anju Gupta, Deepti Suri, Martin de Boer, Taco Kuijpers, Vignesh Pandiarajan, Sapna Sandal, Sebastian Giraldo, Roy Sanguino, Adriana S. Diaz, Selcuk Uzuner, Gizem Durcan, Ali Guven Kilicoglu, Ayhan Bilgic, Kayhan Bahali, Sinem Durmus, Hafize Uzun, Nur Canpolat, Salim Caliskan, Lale Sever, Tomomi Sato, Fuminori Kimura, Wafaa Suwairi, Reem Abdwani, Abdulaziz Al Rowais, Jubran Al qanatish, Abdulrahman Al Asiri, Ekaterina Gaidar, Mikhail Kostik, Elena Serogodskaya, Tatyana Nikitina, Evgenia Isupova, Elham Sardar, Perrine Dusser, Antoine Rousseau, Marc Labetoulle, Emanuel Barreau, Bahram Bodaghi, Isabelle Kone-Paut, Ivan Foeldvari, Jordi Anton, Rosa Bou, Sheila Angeles-Han, Regitze Bangsgaard, Gabriele Brumm, Tamas Constantin, Clive Edelsten, Jens Klotsche, Kirsten Minden, Elisabetta Miserocchi, Susan Nielsen, Gabriele Simonini, Arnd Heiligenhaus, Juan Manuel Mosquera Angarita, Carmen Garcia de Vicuña, Maria Victoria Hernandez, Alfredo Adan, Victor Llorens, Rosa Alcobendas, Susana Noval, Juan Carlos Lopez Robledillo, Isabel Valls, Mari Carmen Pinedo, Alejandro Fonollosa, Jaime de Inocencio, Pilar Tejada, Beatriz Bravo, Manuel Torribio, María Jesús García de Yebenes, Jordi Antón, Uveitis Working Group of the Spanish Pediatric Rheumatology Society, Lorenza Maria Argolini, Irene Pontikaki, Maria Orietta Borghi, Laura Cesana, Barbara Castiglioni, Maurizio Gattinara, Pierluigi Meroni, Pierre Quartier, Veronique Despert, Sylvaine Poignant, Amandine Baptiste, Caroline Elie, Laurent Kodjikian, Dominique Monnet, Michel Weber, Laura Moal, LuuLy Pham, Emmanuel Barreau, Cherif Titah, Pascal Dureau, Vanessa Cecchin, Maria Elisabetta Zannin, Daniele Ferrari, Francesco Comacchio, Rolando Cimaz, Fernanda Falcini, Antonella Petaccia, Stefania Viola, Luciana Breda, Francesco La Torre, Fabio Vittadello, Giorgia Martini, Francesco Zulian, Caroline Galeotti, Guillaume Sarrabay, Olivier Fogel, Isabelle Touitou, Corinne Miceli-Richard, Isabelle Koné-Paut, Hala Etayari, Hashad Soad, Ihab El Kadry, Habibullah Eatamadi, Kais AlAlgawi, Mustafa Al Maini, Khulood Khawaja, Sophie Van den Berghe, Ilse de Schryver, Ann Raes, Lídia L. C. Teixeira, Ana Duarte, Sandra Sousa, Filipe Vinagre, Maria J. Santos, Nataly S. Shevchenko, Ludmila F. Bogmat, Marina V. Demyanenko, Navdha R. Ramchurn, Mark Friswell, Rebecca A. James, Lucy R. Wedderburn, Reshma Pattani, Clarissa A. Pilkington, Sandrine Compeyrot-Lacassagne, Ana V. Villarreal, Nydia Acevedo, Enrique Faugier, Rocio Maldonado, Dilek Yılmaz, Hilal Bektaş Uysal, Elena Kamenets, Ekaterina Zaharova, Stefka Radenska-Lopovok, Joao Nascimento, Helena Sofia, Carla Zilhão, Rui Almeida, Margarida Guedes, Murat Deveci, Svetlana Rodionovskaya, Vera Vinnikova, Irina Tsymbal, Edyta Olesińska, Jacek Postępski, Agnieszka Mroczkowska-Juchkiewicz, Agnieszka Pawłowska-Kamieniak, Beata Chrapko, Damjana Ključevšek, Nina Emeršič, Nataša Toplak, Tadej Avčin, Faina Rokhlina, Galina Glazyrina, Natalia Kolyadina, Kwangnam Kim, Sinae Eom, Daeyoung Kim, Jungwoo Rhim, Francesca Ricci, Paola Montesano, Barbara Bonafini, Veronica Medeghini, Ilaria Parissenti, Antonella Meini, Marco Cattalini, Paolo Airò, Nataliya Panko, Nataliya Shevchenko, Iryna Lebec, Yevgeniya Zajceva, Sara Rostlund, Marie André, Takuma Hara, Takayuki Kishi, Yumi Tani, Aki Hanaya, Satoru Nagata, Velma Selmanovic, Aida Omercahic-Dizdarevic, Adisa Cengic, Almira Cosickic, Aida Omerčahić Dizdarević, Gemma Lepri, Clara Malattia, Eleonora Bellucci, Marco Matucci-Cerinic, Anton Solovyev, Elena Fedotova, Ana Victoria Villarreal, Talia Diaz, Yuridiana Ramirez, Teresa Giani, Achille Marino, Daniel Hunt, Muthana Al Obaidi, Veli Veli, Charalampia Papadopoulou, Jochen Kammermeier, Anna Poluha, Gangadhara C. Bharmappanavara, Alison Kelly, Lindsay Shaw, Giovanna Ferrara, Michele Luzzati, Mattia Giovannini, Liliana Jurado, Juliana Chamorro, Lorena Sarmiento, Ester Conversano, Maria Francesca Gicchino, Giulia Macchini, Carmela Granato, Assunta Tirelli, Alma N. Olivieri, Marija Perica, Lana Tambić Bukovac, Reza Sinaei, Vadood Javadi Parvaneh, Reza Shiari, Khosro Rahmani, Fatemeh F. Mehregan, Mehrnoush Hassas Yeganeh, Inmaculada Calvo Penadés, Berta López Montesinos, Ma Isabel González Fernández, Adriana Rodríguez Vidal, Anand Prahalad Rao, Ayesha Romana, Jyothi Raghuram, Ankur Kumar, Vishali Gupta, Elif Comak, Gülşah Kaya Aksoy, Aygen Yılmaz, Atike Atalay, Mustafa Koyun, Reha Artan, Sema Akman, Maria I. Kaleda, Irina P. Nikishina, Sergei K. Soloviev, Victor A. Malievsky, Ekaterina V. Nikolaeva, Agnieszka Gazda, Beata Kołodziejczyk, Lidia Rutkowska-Sak, Angela Mauro, Pierluigi Marzuillo, Stefano Guarino, and Angela La Manna
Subjects: Pediatrics, RJ1-570, Diseases of the musculoskeletal system, RC925-935
Published: 2017
Full Text: View/download PDF

19. Proceedings of the 23rd Paediatric Rheumatology European Society Congress: part two

Author: Olga Lomakina, Ekaterina Alekseeva, Sania Valieva, Tatiana Bzarova, Irina Nikishina, Elena Zholobova, Svetlana Rodionovskaya, Maria Kaleda, Yasuo Nakagishi, Masaki Shimizu, Mao Mizuta, Akihiro Yachie, Yuko Sugita, Nami Okamoto, Kousuke Shabana, Takuji Murata, Hiroshi Tamai, Eve M. Smith, Peng Yin, Andrea L. Jorgensen, Michael W. Beresford, on behalf of On behalf of the UK JSLE Cohort Study, Antonio Eleuteri, Beatrice Goilav, Laura Lewandowski, Angel Phuti, Dawn Wahezi, Tamar Rubinstein, Caroline Jones, Paul Newland, Stephen Marks, Rachel Corkhill, Diana Ekdawy, Clarissa Pilkington, Kjell Tullus, Chaim Putterman, Chris Scott, Antony C. Fisher, Andrea Jorgensen, Ezgi Deniz Batu, Can Kosukcu, Ekim Taskiran, Sema Akman, Kubra Ozturk, Betul Sozeri, Erbil Unsal, Zelal Ekinci, Yelda Bilginer, Mehmet Alikasifoglu, Seza Ozen, Hanna Lythgoe, Hermine I. Brunner, Gaurav Gulati, Jordan T. Jones, Mekibib Altaye, Jamie Eaton, Mark Difrancesco, Joo Guan Yeo, Jingyao Leong, Loshinidevi D/O Thana Bathi, Thaschawee Arkachaisri, Salvatore Albani, Nagla Abdelrahman, Michael W Beresford, Valentina Leone, UK JSLE study group supported by the National Institute of Health Research Clinical Research Network, Noortje Groot, D. Shaikhani, I. E. M. Bultink, M. Bijl, R. J. E. M. Dolhain, Y. K. O. Teng, E. Zirkzee, K. de Leeuw, R. Fritsch-Stork, S. S. M. Kamphuis, Rachael D. Wright, Reem Abdawani, Laila Al Shaqshi, Ibrahim Al Zakwani, Natali W. Gormezano, David Kern, Oriany L. Pereira, Gladys C. C. Esteves, Adriana M. Sallum, Nadia E. Aikawa, Rosa M. Pereira, Clovis A. Silva, Eloisa Bonfa, Jessica Beckmann, Nora Bartholomä, Nils Venhoff, Philipp Henneke, Ulrich Salzer, Ales Janda, Alina Lucica Boteanu, Sandra Garrote Corral, Alberto Sifuentes Giraldo, Mariluz Gámir Gámir, Antonio Zea Mendoza, Amra Adrovic, Reyhan Dedeoglu, Sezgin Sahin, Kenan Barut, Aida Koka, Funda Oztunc, Ozgur Kasapcopur, Ana Luisa Rodriguez-Lozano, Francisco Rivas-Larrauri, Silvestre García de la Puente, Andressa G. F. Alves, Maria F. D. A. Giacomin, Juliana Farhat, Alfésio L. F. Braga, Adriana M. E. Sallum, Lúcia M. D. A. Campos, Luiz A. A. Pereira, Ana J. D. F. C. Lichtenfels, Clóvis A. Silva, Sylvia C. L. Farhat, Banu Acar, Z. Birsin Ozcakar, Nilgün Çakar, Nermin Uncu, Gökçe Gür, Semanur Özdel, Fatoş Yalçınkaya, Christiaan Scott, Nicky Brice, Peter Nourse, Christine Arango, Angela C. Mosquera, Clara Malagon, Ana P. Sakamoto, Marco F. C. D. Silva, Ananadreia S. Lopes, Gleice C. S. Russo, Adriana E. M. Sallum, Katia Kozu, Eloisa Bonfá, Claudia Saad-Magalhães, Rosa M. R. Pereira, Claudio A. Len, Maria T. Terreri, Deepti Suri, Siyaram Didel, Amit Rawat, Surjit Singh, Despoina Maritsi, MArgarita Onoufriou, Olga Vougiouka, Maria Tsolia, Edi Paleka Bosak, Mandica Vidović, Mirta Lamot, Lovro Lamot, Miroslav Harjaček, Erika Van Nieuwenhove, Adrian Liston, Carine Wouters, Fatemeh Tahghighi, Vahid Ziaee, Seid-Reza Raeeskarami, Francisca Aguiar, Sandra Pereira, Mariana Rodrigues, Cláudia Moura, Gustavo Rocha, Hercília Guimarães, Iva Brito, Rita Fonseca, Gerd Horneff, Ariane Klein, Kirsten Minden, Hans-Iko Huppertz, Frank Weller-Heinemann, Jasmin Kuemmerle-Deschner, J-Peter Haas, Anton Hospach, BIKER collaborative group, Ricardo Menendez-Castro, Boris Huegle, Johannes-Peter Haas, Joost Swart, Gabriella Giancane, Francesca Bovis, Elio Castagnola, Andreas Groll, Daniel J. Lovell, Tom Wolfs, Michael Hofer, Violeta Panaviene, Susan Nielsen, Jordi Anton, Florence Uettwiller, Valda Stanevicha, Maria Trachana, Denise Pires Marafon, Constantin Ailioaie, Elena Tsitsami, Sylvia Kamphuis, Troels Herlin, Pavla Doležalová, Gordana Susic, Berit Flatø, Flavio Sztajnbok, Angela Pistorio, Alberto Martini, Nico Wulffraat, Nicolino Ruperto, Marco Gattorno, Antonio Brucato, Martina Finetti, George Lazaros, Silvia Maestroni, Mara Carraro, Davide Cumetti, Alessandra Carobbio, Monia Lorini, Alessandro Rimini, Renzo Marcolongo, Anna Valenti, Gian Luca Erre, Riccardo Belli, Fiorenzo Gaita, Maria Pia Sormani, Massimo Imazio, Mario Abinun, Nicola Smith, Tim Rapley, Flora McErlane, Lianne Kearsley-Fleet, Kimme L. Hyrich, Helen Foster, Nikolay Tzaribachev, Andrew Zeft, Rolando Cimaz, John Bohnsack, Thomas Griffin, Ruy Carrasco, Jason Dare, Ivan Foeldvari, Richard Vehe, Teresa Simon, Hermine Brunner, S. Verazza, S. Davì, A. Consolaro, A. Insalaco, V. Gerloni, R. Cimaz, F. Zulian, S. Pastore, F. Corona, G. Conti, P. Barone, M. Cattalini, E. Cortis, L. Breda, A. N. Olivieri, A. Civino, R. Podda, D. Rigante, F. La Torre, G. D’Angelo, M. Jorini, R. Gallizzi, M. C. Maggio, R. Consolini, A. De Fanti, M. G. Alpigiani, A. Martini, A. Ravelli, on behalf of Italian Pediatric Rheumatology Study Group, Aysenur Pac Kısaarslan, Zubeyde Gunduz, Ruhan Dusunsel, Ismail Dursun, Hakan Poyrazoglu, Ekaterina Kuchinskaya, Farida Abduragimova, Mikhail Kostik, Erik Sundberg, Soley Omarsdottir, Lena Klevenvall, Helena Erlandsson-Harris, Gokalp Basbozkurt, Ozge Erdemli, Dogan Simsek, Fatih Yazici, Yildirim Karsioglu, Aysen Tezcaner, Dilek Keskin, Huseyin Ozkan, Cengizhan Acikel, Erkan Demirkaya, Ilonka Orbán, Krisztina Sevcic, Valentin Brodszky, Emese Kiss, Ismaiel A. Tekko, Madeleine Rooney, James McElnay, Cliff Taggart, Helen McCarthy, Ryan F. Donnelly, Drug Delivery Group, Mary Slatter, Zohreh Nademi, Mark Friswell, Sharmila Jandial, Terence Flood, Sophie Hambleton, Andrew Gennery, Andrew Cant, Phoi-Ngoc Duong, Isabelle Koné-Paut, Giovanni Filocamo, María Luz Gamir, Helga Sanner, Laura Carenini, Mesut Topdemir, Yildirim Karslioglu, Faysal Gok, Nadezhda Tsurikova, Elena Ligostaeva, Navdha R. Ramchurn, O. Kostareva, I. Nikishina, S. Arsenyeva, S. Rodionovskaya, M. Kaleda, D. Alexeev, Ismail Dursun Dursun, Sara Murias, Estefania Barral, Rosa Alcobendas, Eugenia Enriquez, Agustin Remesal, Jaime de Inocencio, Tania M. Castro, Simone A. Lotufo, Tatjana Freye, Raffaella Carlomagno, Thomas Zumbrunn, Jan Bonhoeffer, Elvira Cannizzaro Schneider, Daniela Kaiser, Michaël Hofer, Véronique Hentgen, Andreas Woerner, Juvenile Inflammatory Rheumatism (JIR) Cohort, Tobias Schwarz, Jens Klotsche, Martina Niewerth, Gerd Ganser, ICON study group, Jerold Jeyaratnam, Nienke ter Haar, Donato Rigante, Fatma Dedeoglu, Ezgi Baris, Sebastiaan Vastert, Joost Frenkel, Jonathan S. Hausmann, Kathleen G. Lomax, Ari Shapiro, Karen L. Durrant, P. A. Brogan, M. Hofer, J. B. Kuemmerle-Deschner, B. Lauwerys, A. Speziale, K. Leon, X. Wei, R. M. Laxer, Sara Signa, Marta Rusmini, Elena Campione, Sabrina Chiesa, Alice Grossi, Alessia Omenetti, Roberta Caorsi, Gianmaria Viglizzo, Isabella Ceccherini, Silvia Federici, Helen Lachmann, Nicola Ruperto, on behalf of PRINTO and Eurofever Registry, Federica Vanoni, on behalf of PRINTO and Eurofever Project, Sonia Melo Gomes, Ebun Omoyinmi, Juan I. Arostegui, Eva Gonzalez-Roca, Despina Eleftheriou, Nigel Klein, Paul Brogan, Stefano Volpi, Elettra Santori, Paolo Picco, Claudia Pastorino, Gillian Rice, Alessandra Tesser, Yanick Crow, Fabio Candotti, Ada B. Sinoplu, Gozde Yucel, Gizem Pamuk, Laura O. Damian, Cecilia Lazea, Mihaela Sparchez, Paulina Vele, Laura Muntean, Adriana Albu, Simona Rednic, Calin Lazar, Leonardo O. Mendonça, Alessandra Pontillo, Jorge Kalil, Fabio M. Castro, Myrthes T. Barros, Manuela Pardeo, Virginia Messia, Fabrizio De Benedetti, Antonella Insalaco, Giorgia Malighetti, Chiara Gorio, Francesca Ricci, Ilaria Parissenti, Paola Montesano, Barbara Bonafini, Veronica Medeghini, Marco Cattalini, Lucio Giordano, Giulia Zani, Rosalba Ferraro, Donatella Vairo, Silvia Giliani, Maria Cristina Maggio, Girolamo Luppino, Giovanni Corsello, Maria Isabel Gonzalez Fernandez, Berta Lopez Montesinos, Adriana Rodriguez Vidal, Juan I. Arostegui Gorospe, Inmaculada Calvo Penades, Nadia K. Rafiq, Karen Wynne, Khalid Hussain, Paul A. Brogan, Elizabeth Ang, Nicholas Ng, Ayla Kacar, Ozge Altug Gucenmez, Balahan Makay, Sevket Erbil Unsal, Yasin Sahin, Tufan Kutlu, Fugen Cullu-Cokugras, Hasret Ayyildiz-Civan, Tulay Erkan, Sana Al Zuhbi, Eiman Abdalla, Ricardo A. Russo, María M. Katsicas, Francesca Minoia, Angelo Ravelli, Sagar Bhattad, Anju Gupta, Vignesh Pandiarajan, Ritambhra Nada, Kaara Tiewsoh, Philip Hawkins, Dorota Rowczenio, Sarka Fingerhutova, Jana Franova, Leona Prochazkova, Eva Hlavackova, Pavla Dolezalova, Havva Evrengül, Selçuk Yüksel, Mustafa Doğan, Dolunay Gürses, Harun Evrengül, Silvia De Pauli, Serena Pastore, Anna Monica Bianco, Giovanni Maria Severini, Andrea Taddio, Alberto Tommasini, Svetlana O. Salugina, Evgeny Fedorov, Elena Kamenets, Ekaterina Zaharova, Tatiana Sleptsova, Ekaterina Alexeeva, Kirill Savostyanov, Alexander Pushkov, Tatyana Bzarova, Saniya Valieva, Rina Denisova, Kseniya Isayeva, Evgeniya Chistyakova, Margarita Soloshenko, Elena Kaschenko, Utako Kaneko, Chihaya Imai, Akihiko Saitoh, Vitor A. Teixeira, Filipa O. Ramos, Manuela Costa, Yonatan Butbul Aviel, Shafe Fahoum, Riva Brik, Zeynep Birsin Özçakar, Banu Acar Celikel, Fatos Yalcinkaya, Benedetta Schiappapietra, Sergio Davi’, Federica Mongini, Luisa Giannone, Cecilia Bava, Maria Giannina Alpigiani, Alessandro Consolaro, Dragana S. Lazarevic, Jelena Vojinovic, Jelena Basic, Valentina Muratore, Valentina Marzetti, Neus Quilis, Belen Serrano Benavente, Alessandra Alongi, Adele Civino, Lorenzo Quartulli, Giedre Januskeviciute, Pieter van Dijkhuizen, N. Groot, W. van Dijk, A. Kardolus, Raul Gutiérrez Suárez, Ellen B. Nordal, Veronika G. Rypdal, Lillemor Berntson, Maria Ekelund, Kristiina Aalto, Suvi Peltoniemi, Marek Zak, Mia Glerup, Ellen D. Arnstad, Anders Fasth, Marite Rygg, the Nordic Study Group of Pediatric Rheumatology (NoSPeR), Ana Catarina Duarte, Sandra Sousa, Lídia Teixeira, Ana Cordeiro, Mª José Santos, Ana Filipa Mourão, Maria José Santos, Mónica Eusébio, Ana Lopes, Filipa Oliveira-Ramos, Manuel Salgado, Paula Estanqueiro, José Melo-Gomes, Fernando Martins, José Costa, Carolina Furtado, Ricardo Figueira, Jaime C. Branco, João E. Fonseca, Helena Canhão, Ana F. Mourão, Maria Jose Santos, Andrea Coda, Samuel Cassidy, Kerry West, Gordon Hendry, Debra Grech, Julie Jones, Fiona Hawke, Davinder Singh Grewal, Charlene Foley, Orla Killeen, Emma MacDermott, Douglas Veale, Ursula Fearon, Dilek Konukbay, Ela Tarakci, Nilay Arman, Sezgin Şahin, Jane Munro, Esi Morgan, Meredith Riebschleger, Jennifer Horonjeff, Vibeke Strand, Clifton Bingham, Ma. Theresa M. Collante, Margarita Ganeva, Stefan Stefanov, Albena Telcharova, Dimitrina Mihaylova, Radoslava Saraeva, Reni Tzveova, Radka Kaneva, Adelina Tsakova, Katya Temelkova, GRANT Medical University, Sofia 68/, Maria Mercedes C. Picarelli, Luiz C. Danzmann, Florencia Barbé-Tuana, Lucas K. Grun, Marcus H. Jones, Marijan Frković, Karla Ištuk, Ika Birkić, Saša Sršen, Marija Jelušić, Alan Easton, Rachael Quarmby, Raju Khubchandani, Mercedes Chan, Radoslav Srp, Katerina Kobrova, Dana Nemcova, Jozef Hoza, Michal Uher, Melania Saifridova, Lenka Linkova, Sirirat Charuvanij, Isree Leelayuwattanakul, Thita Pacharapakornpong, Sakda A.-O. Vallipakorn, Butsabong Lerkvaleekul, Soamarat Vilaiyuk, Stefano Lanni, Sergio Davì, Randy Q. Cron, Chiara Passarelli, Elisa Pisaneschi, Antonio Novelli, Claudia Bracaglia, Ivan Caiello, Kathy de Graaf, Florence Guilhot, Walter Ferlin, Grant Schulert, Alexi A. Grom, Robert Nelson, Cristina de Min, Dirk Holzinger, Christoph Kessel, Ndate Fall, Alexei Grom, Wilco de Jager, Raffaele Strippoli, Anna Horne, Stephan Ehl, Sandra Ammann, Kai Lehmberg, Karin Beutel, Dirk Foell, AnnaCarin Horne, Laura Pagani, Graciela Espada, Yi-jin Gao, Susan Shenoi, Sheila Weitzman, Giusi Prencipe, Antonia Pascarella, Walter G. Ferlin, Laurence Chatel, Philippe Jacqmin, Kathy De Graaf, Maria Ballabio, Zoë Johnson, Geneviève Lapeyre, Fabrizio de Benedetti, de Min Cristina, Hiroyuki Wakiguchi, Shunji Hasegawa, Reiji Hirano, Fumiko Okazaki, Tamaki Nakamura, Hidenobu Kaneyasu, Shouichi Ohga, Kazuko Yamazaki, Tomo Nozawa, Taichi Kanetaka, Shuichi Ito, Shumpei Yokota, Kirsty McLellan, Ishbel MacGregor, Neil Martin, Joyce Davidson, Sandra Hansmann, Andreas Eikelberg, Iris Haug, Sabrina Schuller, Susanne M. Benseler, Single Hub and Access point for paediatric Rheumatology in Europe (SHARE), Liliia S. Nazarova, Kseniia V. Danilko, Viktor A. Malievsky, Tatiana V. Viktorova, Angela Mauro, Angela Barnicoat, Jane Hurst, Nathalie Canham, Sandrine Lacassagne, Anastasia Wiener, Boris Hügle, Bernd Denecke, Ivan Costa-Filho, Johannes Peter Haas, Klaus Tenbrock, David Popp, Arjan Boltjes, Frank Rühle, Stefanie Herresthal, Femke van Wijk, Joachim Schultze, Monika Stoll, Luisa Klotz, Thomas Vogl, Johannes Roth, Estefania Quesada-Masachs, Daniel Álvarez de la Sierra, Marina Garcia Prat, Ana M. Marín Sánchez, Ricardo Pujol Borrell, Sara Marsal Barril, Mónica Martínez Gallo, Consuelo Modesto Caballero, Iryna Chyzheuskaya, Lyudmyla M. Byelyaeva, Rostislav M. Filonovich, Helena K. Khrustaleva, Larisa I. Zajtseva, Tamara M. Yuraga, Thomas Giner, Lukas Hackl, Julia Albrecht, Reinhard Würzner, Juergen Brunner, Marta Minute, Fulvio Parentin, Agostino Nocerino, Mette Nørgaard, Mikel Alberdi-Saugstrup, Marek S. Zak, Susan M. Nielsen, Ellen Nordal, Klaus G. Müller, Nordic Study Group of Pediatric Rheumatology (NoSPeR), Mojca Zajc Avramovič, Vita Dolžan, Nataša Toplak, Tadej Avčin, N. Ruperto, D. J. Lovell, C. Wallace, M. Toth, I. Foeldvari, J. Bohnsack, D. Milojevic, C. Rabinovich, D. Kingsbury, K. Marzan, P. Quartier, K. Minden, E. Chalom, G. Horneff, R. M. Kuester, J. Dare, M. Heinrich, H. Kupper, J. Kalabic, H. I. Brunner, on behalf of PRINTO and PRCSG, Ruben Burgos-Vargas, Tamas Constantin, Joke Dehoorne, Valda Stanevica, Katarzyna Kobusinska, Zbigniew Zuber, Richard Mouy, Ingrida Rumba-Rozenfelde, Chantal Job-Deslandre, Ronald Pederson, Jack Bukowski, Tina Hinnershitz, Bonnie Vlahos, Paula Keskitalo, Salla Kangas, Paula Vähäsalo, Raul A. Chavez Valencia, David Martino, Anne-Louise Ponsonby, Rachel Chiaroni-Clarke, Braydon Meyer, Roger C. Allen, Jonathan D. Akikusa, Jeffrey M. Craig, Richard Saffrey, Justine A. Ellis, Carol Wallace, Yosef Uziel, Gary Sterba, Rayfel Schneider, Ricardo Russo, Athimalaipet V. Ramanan, Jana Pachlopnik Schmid, Kim E Nichols, Paivi Miettunen, Toshiyuki Kitoh, Norman T. Ilowite, Jan-Inge Henter, Alexei A Grom, Edward M. Behrens, Tadej Avcin, Maurizio Aricò, Sriharsha Grevich, Peggy Lee, Sarah Ringold, Brian Leroux, Hannah Leahey, Megan Yuasa, Jessica Foster, Jeremy Sokolove, Lauren Lahey, William Robinson, Joshua Newson, Anne Stevens, Stephanie J. W. Shoop, Suzanne M. M. Verstappen, Wendy Thomson, Janet E. McDonagh, CAPS, Timothy Beukelman, Yuki Kimura, Marc Natter, Norm Ilowite, Kelly Mieszkalski, Grendel Burrell, Brian Best, Helen Bristow, Shannon Carr, Anne Dennos, Rachel Kaufmann, Laura Schanberg, for the CARRA Registry Investigators, Gabriele Simonini, Francesca Lancini, Margaux Gerbaux, Phu-Quoc Lê, Laurence Goffin, Valérie Badot, Céline La, Laure Caspers, François Willermain, Alina Ferster, Maria Ceci, Francesco Licciardi, Marco Turco, Francesca Santarelli, Davide Montin, Claudia Toppino, Clotilde Alizzi, Bruno Papia, Beatrice Vergara, Umberto Corpora, Luca Messina, Maria Tsinti, Vasiliko Dermentzoglou, Panagiotis Tziavas, Marija Perica, Lana Tambić Bukovac, Mustafa Çakan, Nuray Aktay Ayaz, Gonca Keskindemirci, Michael Lang, Catherine Laing, Susanne Benseler, Tommy Gerschman, Nadia Luca, Heinrike Schmeling, Anastasia Dropol, Jaymi Taiani, Nicole Johnson, Brian Rusted, Panagiota Nalbanti, Polyxeni Pratsidou, Grigoris Pardalos, Vasiliki Tzimouli, Anna Taparkou, Maria Stavrakidou, Fotios Papachristou, Florence Kanakoudi-Tsakalidou, Peter Bale, Emily Robinson, Jason Palman, Elizabeth Ralph, Kimberly Gilmour, Clare Heard, Lucy R. Wedderburn, Yara Barrense-Dias, Antonarakis Gregory, Dhouib Amira, Scolozzi Paolo, Hanquinet Sylviane, Hofer Michaël, Nataliya Panko, Salah Shokry, Liudmila Rakovska, Sally Pino, Adriana Diaz-Maldonado, Pilar Guarnizo, Sofia Torreggiani, Paolo Cressoni, Umberto Garagiola, Giancarla Di Landro, Giampietro Farronato, Fabrizia Corona, Samantha Bell, Parveen Bhatti, Lee Nelson, Beth A. Mueller, T. A. Simon, A. Baheti, N. Ray, Z. Guo, Anasuya Hazra, Thomas Stock, Ronnie Wang, Charles Mebus, Christine Alvey, Manisha Lamba, Sriram Krishnaswami, Umberto Conte, Min Wang, Daniel Kingsbury, Elena Koskova, Elzbieta Smolewska, Richard K. Vehe, Daniel Lovell, Tomohiro Kubota, Junko Yasumura, Toshitaka Kizawa, Masato Yashiro, Tsuyoshi Yamatou, Yuichi Yamasaki, Syuji Takei, Yoshifumi Kawano, Ulrika Järpemo Nykvist, Bo Magnusson, Rikard Wicksell, Karin Palmblad, Gunnar L. Olsson, Mohammadreza Modaressi, Mohammad-Hassan Moradinejad, Valentina Seraya, Alisa Vitebskaya, Veronica Moshe, Gil Amarilyo, Liora Harel, Phillip J Hashkes, Amir Mendelson, Noa Rabinowicz, Yonit Reis, Zane Dāvidsone, Arina Lazareva, Ruta Šantere, Dace Bērziņa, Valda Staņēviča, Giulia Camilla Varnier, Susan Maillard, Cristina Ferrari, Silvia Zaffarano, Juvenile Dermatomyositis Research Group and European Federation of Immunological Societies, Judith Wienke, Felicitas Bellutti Enders, Lucas L. van den Hoogen, Jorre S. Mertens, Timothy R. Radstake, Henny G. Hotten, Ruth Fritsch, Lucy Wedderburn, Kiran Nistala, Berent Prakken, Annet van Royen-Kerkhof, Mohammad Alhemairi, Mohammed Muzaffer, Pieter Van Dijkhuizen, Claire T. Deakin, Stefania Simou, Maria De Iorio, Qiong Wu, Tania Amin, Lee Dossetter, Juvenile Dermatomyositis Research Group (JDRG), Raquel Campanilho-Marques, Claire Deakin, Clarissa A. Pilkington, on behalf of Juvenile Dermatomyositis Research Group (JDRG), Silvia Rosina, Sirisucha Soponkanaporn, on behalf of the UK Juvenile Dermatomyositis Research Group (JDRG), Zehra S. Arıcı, Gökçen D. Tuğcu, Ezgi D. Batu, Hafize E. Sönmez, Deniz Doğru-Ersöz, Beril Talim, Nural Kiper, Seza Özen, Alexander Solyom, Ezgi Batu, John Mitchell, Ariana Kariminejad, Fatemeh Hadipour, Zahra Hadipour, Marta Torcoletti, Carlo Agostoni, Maja Di Rocco, Pranoot Tanpaiboon, Andrea Superti-Furga, Luisa Bonafé, Nur Arslan, Norberto Guelbert, Karoline Ehlert, Giedre Grigelioniene, Ratna Puri, Edward Schuchman, Pilar Gomez, Tatiana Gonzalez, Ricardo Yepez, Camilo Vargas, GRIP study group, Falcini Fernanda, Gemma Lepri, Alessandra Ferrari, Marco Matucci-Cerinic, Antonella Meini, Gian Marco Moneta, Emiliano Marasco, Rebecca Nicolai, Luisa Bracci-Laudiero, Olga Kopchak, Alexander Mushkin, Alexey Maletin, Catalina Mosquera, Rita A. Amorim, Juliana Molina, Gustavo Moreira, Flávia H. Santos, Melissa Fraga, Livia Keppeke, Vanessa M. Silva, Camila Hirotsu, Sergio Tufik, Maria Teresa Terreri, Vinícius L. Braga, Maria Beatriz Fonseca, Vania Schinzel, Maria Teresa R. Terreri, Liliana Jorge, Liana Guerra, Edson Amaro Junior, Maria Cristina Castiglione, Alessandra Tricarico, Emily Boulter, Andre Schultz, Kevin Murray, Fernanda Falcini, Stefano Stagi, Eleonora Bellucci, Ingrid H. R. Grein, Gecilmara Pileggi, Natália B. F. Pinto, Aline L. de Oliveira, Lyudmila Belyaeva, Rostislav Filonovich, Helena Khrustaleva, Larisa Zajtseva, Jaanika Ilisson, Chris Pruunsild, Olivier Gilliaux, Francis Corazza, Christophe Lelubre, on behalf of PANLAR Pediatric Rheumatology Study Group, Zoilo Morel, Claudia Saad-Magalhães C, Luis Lira, Mabel Ladino, Ruth Eraso, Ivonne Arroyo, Clovis Silva, Carlos Rose, and PANLAR Pediatric Rheumatology Study Group
Subjects: Pediatrics, RJ1-570, Diseases of the musculoskeletal system, RC925-935
Published: 2017
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20. Driving Medical Innovation Through Interdisciplinarity: Unique Opportunities and Challenges

Author: Faekah Gohar, Patrick Maschmeyer, Bechara Mfarrej, Mathieu Lemaire, Lucy R. Wedderburn, Maria Grazia Roncarolo, and Annet van Royen-Kerkhof
Subjects: interdiscipinarity, societal impact, translational medical research, innovation, collaboration, Medicine (General), R5-920
Published: 2019
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21. Sex and Pubertal Differences in the Type 1 Interferon Pathway Associate With Both X Chromosome Number and Serum Sex Hormone Concentration

Author: Kate Webb, Hannah Peckham, Anna Radziszewska, Madhvi Menon, Paola Oliveri, Fraser Simpson, Claire T. Deakin, Sophie Lee, Coziana Ciurtin, Gary Butler, Lucy R. Wedderburn, and Yiannis Ioannou
Subjects: interferon, TLR7, immunity, sex, puberty, SLE, Immunologic diseases. Allergy, RC581-607
Abstract: Type 1 interferons (IFN) are an antiviral cytokine family, important in juvenile onset systemic lupus erythematosus (jSLE) which is more common in females, around puberty. We report that plasmacytoid dendritic cells (pDC) from healthy females produced more type 1 IFN after toll like receptor (TLR) 7 signaling than males, even before puberty, but that puberty itself associated with increased production of type 1 IFN. A unique human model allows us to show that this was related to X chromosome number, and serum testosterone concentration, in a manner which differed depending on the number of X chromosomes present. In addition, we have showed that pDC were more activated in females overall, and immune cell TLR7 gene expression was higher in females after puberty. Therefore, sex hormones and X chromosome number were associated individually and interactively with the type 1 IFN response, which contributes to our understanding of why females are more likely to develop an IFN mediated disease like jSLE after puberty.
Published: 2019
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22. Systemic and Tissue Inflammation in Juvenile Dermatomyositis: From Pathogenesis to the Quest for Monitoring Tools

Author: Judith Wienke, Claire T. Deakin, Lucy R. Wedderburn, Femke van Wijk, and Annet van Royen-Kerkhof
Subjects: juvenile dermatomyositis, tissue inflammation, vasculopathy, disease monitoring, biomarkers, interferon signature, Immunologic diseases. Allergy, RC581-607
Abstract: Juvenile Dermatomyositis (JDM) is a systemic immune-mediated disease of childhood, characterized by muscle weakness, and a typical skin rash. Other organ systems and tissues such as the lungs, heart, and intestines can be involved, but may be under-evaluated. The inflammatory process in JDM is characterized by an interferon signature and infiltration of immune cells such as T cells and plasmacytoid dendritic cells into the affected tissues. Vasculopathy due to loss and dysfunction of endothelial cells as a result of the inflammation is thought to underlie the symptoms in most organs and tissues. JDM is a heterogeneous disease, and several disease phenotypes, each with a varying combination of affected tissues and organs, are linked to the presence of myositis autoantibodies. These autoantibodies have therefore been extensively studied as biomarkers for the disease phenotype and its associated prognosis. Next to identifying the JDM phenotype, monitoring of disease activity and disease-inflicted damage not only in muscle and skin, but also in other organs and tissues, is an important part of clinical follow-up, as these are key determinants for the long-term outcomes of patients. Various monitoring tools are currently available, among which clinical assessment, histopathological investigation of muscle and skin biopsies, and laboratory testing of blood for specific biomarkers. These investigations also give novel insights into the underlying immunological processes that drive inflammation in JDM and suggest a strong link between the interferon signature and vasculopathy. New tools are being developed in the quest for minimally invasive, but sensitive and specific diagnostic methods that correlate well with clinical symptoms or reflect local, low-grade inflammation. In this review we will discuss the types of (extra)muscular tissue inflammation in JDM and their relation to vasculopathic changes, critically assess the available diagnostic methods including myositis autoantibodies and newly identified biomarkers, and reflect on the immunopathogenic implications of identified markers.
Published: 2018
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23. Juvenile dermatomyositis. Where are we now?

Author: Liza J. McCann, Polly Livermore, Meredyth G.Ll. Wilkinson, and Lucy R. Wedderburn
Subjects: Myositis, Rheumatology, Immunology, Disease Progression, Quality of Life, Humans, Immunology and Allergy, Vascular Diseases, Dermatomyositis
Abstract: Juvenile onset idiopathic inflammatory myopathy (IIM) has many similarities and distinct differences from adult-onset disease. This review will focus on recent developments in understanding and treatment of juvenile dermatomyositis (JDM), the most common disease sub-type of IIM in childhood. JDM is a systemic immune mediated vasculopathy, increasingly recognised as a group of distinct phenotypes with variable presentation and outlook. This overview will describe long-term outlook and disease course including health-related quality of life and emerging treatments.
Published: 2022

24. 100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care — Preliminary Report

Author: Gill Wilson, Anna de Burca, Marta Bleda, Lucy R. Wedderburn, Matthew Welland, Kathleen Stirrups, Valentina Cipriani, Kerrie Woods, Vijeya Ganesan, Susan Hill, Rosaline Quinlivan, Georgia Chan, Mehul T. Dattani, Robert McFarland, Graeme C.M. Black, Rutendo Mapeta, Augusto Rendon, Francesco Muntoni, James O.J. Davies, Mina Ryten, Rebecca E. Foulger, Arianna Tucci, Dina Halai, Tom Fowler, Noemi B.A. Roy, Sarah Leigh, Dragana Josifova, Philip Twiss, Ana L.T. Tavares, Zerin Hyder, Detlef Bockenhauer, Patrick Yu-Wai-Man, Lara Abulhoul, Nikolas Pontikos, Anthony T. Moore, Huw R. Morris, Patrick F. Chinnery, Nicholas W. Wood, Ellen A. Thomas, Shehla Mohammed, Sofia Douzgou, Tanya Lam, Kate Gibson, Robert Sarkany, Teofila Bueser, Wei Wei, Siddharth Banka, Alexander Broomfield, Hiva Fassihi, Nils Koelling, Carolyn Campbell, James Buchanan, Melita Irving, Sandrine Compeyrot-Lacassagne, Karola Rehmström, Austen Worth, Nikhil Thapar, Andrew R. Webster, Paul Brennan, Rita Horvath, Gavin Arno, Richard H Scott, Sam Malka, Andrew O.M. Wilkie, Sofie Ashford, Maria Bitner-Glindzicz, Jana Vandrovcova, William G. Newman, Caroline F. Wright, Andrew M. Schaefer, Roger F.L. James, Robert W. Taylor, Melanie Babcock, Arjune Sen, Emma Baple, Ellen M. McDonagh, Stephanie Grunewald, Loukas Moutsianas, Melissa A. Haendel, Olivera Spasic-Boskovic, Eleanor G. Seaby, Anna Need, Clarissa Pilkington, Sarah Wordsworth, Shamima Rahman, Christine Patch, Colin Wallis, Kristina Ibanez, Bishoy Habib, Eik Haraldsdottir, Huw B. Thomas, Razvan Sultana, Andrea H. Németh, Agata Wolejko, Claire Palles, Phil Beales, Adam C. Shaw, Letizia Vestito, Emily Li, Sarah Rose, Sarah Hunter, Angela Matchan, Genevieve Say, Dalia Kasperaviciute, Henry Houlden, Raymond T. O’Keefe, R. Andres Floto, Jill Clayton-Smith, John B. Taylor, Hywel J. Williams, Volker Straub, Val Davison, Helen Savage, John Chisholm, Eleanor Dewhurst, Charles Crichton, Andrea Haworth, Clare Turnbull, Carolyn Tregidgo, Carme Camps, Christopher Penkett, Emer O’Connor, Georgina Hall, Lyn S. Chitty, Sally Halsall, Andrew D. Mumford, Annette G. Wagner, Eleanor Williams, Mark Bale, Julius O. Jacobsen, Willem H. Ouwehand, Charu Deshpande, Gavin Burns, Smita Y. Patel, James Polke, Thiloka Ratnaike, Gavin Fuller, John Burn, Kenneth E. S. Poole, Emma Footitt, John R. Bradley, Suzanne Wood, Russell J. Grocock, Jenny C. Taylor, Louise Izatt, Kikkeri N. Naresh, Katherine R. Smith, Nigel Burrows, Katrina Newland, Peter N. Robinson, Sarju G. Mehta, Michael A. Simpson, Michael R. Barnes, Pilar Cacheiro, Olivia Niblock, Tracy Lester, Dimitris Polychronopoulos, Helen Brittain, John A. Sayer, Antonio Martin, Eshika Haque, Sean Humphray, Douglass M. Turnbull, Damian Smedley, Andrew Devereau, Stefan Gräf, Sian Ellard, Ivone U.S. Leong, Martin G. Reese, Matthias Wielscher, Louise C. Daugherty, Perry M. Elliott, F. Lucy Raymond, Cecilia Compton, David Bentley, Catherine Snow, James Welch, Frances Flinter, Dom McMullan, Mark J. Caulfield, Paul Aurora, Mark Gurnell, Mary Kasanicki, I. Karen Temple, Michel Michaelides, Deborah Ruddy, Leema Robert, Janice Yip, Grainne S. Gorman, Andrew C. Browning, Richard Quinton, Maureen Cleary, Jamie M. Ellingford, Angela Douglas, Christopher Boustred, and Investigators, The 100,000 Genomes Project Pilot
Subjects: Adult, Male, Proband, medicine.medical_specialty, Adolescent, Pilot Projects, Genomics, Polymerase Chain Reaction, Genome, State Medicine, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Health care, Human Phenotype Ontology, Humans, Medicine, Child, Exome sequencing, 030304 developmental biology, Family Characteristics, 0303 health sciences, Whole Genome Sequencing, Genome, Human, business.industry, Genetic Variation, Rare Diseases/diagnosis, General Medicine, Middle Aged, United Kingdom, 3. Good health, Child, Preschool, Family medicine, Medical genetics, Female, business, Bristol, 030217 neurology & neurosurgery, Rare disease
Abstract: BACKGROUND: The U.K. 100,000 Genomes Project is in the process of investigating the role of genome sequencing in patients with undiagnosed rare diseases after usual care and the alignment of this research with health care implementation in the U.K. National Health Service. Other parts of this project focus on patients with cancer and infection.METHODS: We conducted a pilot study involving 4660 participants from 2183 families, among whom 161 disorders covering a broad spectrum of rare diseases were present. We collected data on clinical features with the use of Human Phenotype Ontology terms, undertook genome sequencing, applied automated variant prioritization on the basis of applied virtual gene panels and phenotypes, and identified novel pathogenic variants through research analysis.RESULTS: Diagnostic yields varied among family structures and were highest in family trios (both parents and a proband) and families with larger pedigrees. Diagnostic yields were much higher for disorders likely to have a monogenic cause (35%) than for disorders likely to have a complex cause (11%). Diagnostic yields for intellectual disability, hearing disorders, and vision disorders ranged from 40 to 55%. We made genetic diagnoses in 25% of the probands. A total of 14% of the diagnoses were made by means of the combination of research and automated approaches, which was critical for cases in which we found etiologic noncoding, structural, and mitochondrial genome variants and coding variants poorly covered by exome sequencing. Cohortwide burden testing across 57,000 genomes enabled the discovery of three new disease genes and 19 new associations. Of the genetic diagnoses that we made, 25% had immediate ramifications for clinical decision making for the patients or their relatives.CONCLUSIONS: Our pilot study of genome sequencing in a national health care system showed an increase in diagnostic yield across a range of rare diseases. (Funded by the National Institute for Health Research and others.).
Published: 2021

25. CD19+CD24hiCD38hi B Cells Are Expanded in Juvenile Dermatomyositis and Exhibit a Pro-Inflammatory Phenotype After Activation Through Toll-Like Receptor 7 and Interferon-α

Author: Christopher J. M. Piper, Meredyth G. Ll. Wilkinson, Claire T. Deakin, Georg W. Otto, Stefanie Dowle, Chantal L. Duurland, Stuart Adams, Emiliano Marasco, Elizabeth C. Rosser, Anna Radziszewska, Rita Carsetti, Yiannis Ioannou, Philip L. Beales, Daniel Kelberman, David A. Isenberg, Claudia Mauri, Kiran Nistala, and Lucy R. Wedderburn
Subjects: immature transitional B cells, B cells, juvenile dermatomyositis, toll-like receptor 7, interferon alpha, interleukin-10, Immunologic diseases. Allergy, RC581-607
Abstract: Juvenile dermatomyositis (JDM) is a rare form of childhood autoimmune myositis that presents with proximal muscle weakness and skin rash. B cells are strongly implicated in the pathogenesis of the disease, but the underlying mechanisms are unknown. Therefore, the main objective of our study was to investigate mechanisms driving B cell lymphocytosis and define pathological features of B cells in JDM patients. Patients were recruited through the UK JDM Cohort and Biomarker study. Peripheral blood B cell subpopulations were immunophenotyped by flow cytometry. The results identified that immature transitional B cells were significantly expanded in active JDM, actively dividing, and correlated positively with disease activity. Protein and RNAseq analysis revealed high interferon alpha (IFNα) and TLR7-pathway signatures pre-treatment. Stimulation of B cells through TLR7/8 promoted both IL-10 and IL-6 production in controls but failed to induce IL-10 in JDM patient cells. Interrogation of the CD40–CD40L pathway (known to induce B cell IL-10 and IL-6) revealed similar expression of IL-10 and IL-6 in B cells cultured with CD40L from both JDM patients and controls. In conclusion, JDM patients with active disease have a significantly expanded immature transitional B cell population which correlated with the type I IFN signature. Activation through TLR7 and IFNα may drive the expansion of immature transitional B cells in JDM and skew the cells toward a pro-inflammatory phenotype.
Published: 2018
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26. Genome-wide imputation identifies novel associations and localises signals in idiopathic inflammatory myopathies

Author: Simon, Rothwell, Christopher I, Amos, Frederick W, Miller, Lisa G, Rider, Ingrid E, Lundberg, Peter K, Gregersen, Jiri, Vencovsky, Neil, McHugh, Vidya, Limaye, Albert, Selva-O'Callaghan, Michael G, Hanna, Pedro M, Machado, Lauren M, Pachman, Ann M, Reed, Øyvind, Molberg, Olivier, Benveniste, Pernille, Mathiesen, Timothy, Radstake, Andrea, Doria, Jan L, De Bleecker, Boel, De Paepe, Britta, Maurer, William E, Ollier, Leonid, Padyukov, Terrance P, O'Hanlon, Annette, Lee, Lucy R, Wedderburn, Hector, Chinoy, Janine A, Lamb, and Richard J, Barohn
Abstract: The idiopathic inflammatory myopathies (IIM) are heterogeneous diseases, thought to be initiated by immune activation in genetically predisposed individuals. In this study we imputed variants from the Immunochip array using a large reference panel to fine-map associations and identify novel associations in IIM.We analysed 2,565 Caucasian IIM samples collected through the Myositis Genetics Consortium (MYOGEN) and 10,260 ethnically-matched controls. We imputed 1,648,116 variants from the Immunochip array using the Haplotype Reference Consortium panel and conducted association analysis on IIM, and clinical and serological subgroups.The human leukocyte antigen (HLA) locus was consistently the most significantly associated region. Four non-HLA regions reached genome-wide significance, three in the whole IIM cohort (SDK2 and LINC00924 - both novel, and STAT4), with evidence of independent variants in STAT4, and NAB1 in the polymyositis (PM) subgroup. We also found suggestive evidence of association with loci previously associated with other autoimmune rheumatic diseases (TEC and LTBR). We identified more significant associations than those previously reported in IIM, for STAT4 and DGKQ in the total cohort, for NAB1 and FAM167A-BLK loci in PM, and CCR5 in inclusion body myositis. We found enrichment of variants among DNase I hypersensitivity sites and histone marks associated with active transcription within blood cells.We report novel and strong associations in IIM and PM, and localise signals to single genes and immune cell types. This article is protected by copyright. All rights reserved.
Published: 2022

27. OA29 Blotting-based assays under-detected TIF1-gamma and NXP2 autoantibodies compared to immunoprecipitation in Juvenile Dermatomyositis cohorts

Author: Huong D Nguyen, Charalampia Papadopoulou, Dario Cancemi, Lucy R Wedderburn, and Sarah L Tansley
Subjects: Rheumatology
Abstract: Introduction/Background The rare heterogenous autoimmune disease Juvenile Dermatomyositis (JDM) relies on prognostic tools including myositis specific antibodies (MSA) and myositis associated antibodies (MAA) to guide early treatment and reduce the risks of poor outcome. However, there is an emerging concern regarding the inter-assay validity due to the current lack of a standardised protocol for MSA/MAA screening across healthcare centres. Among available MSA/MAA screening assays, most laboratories prefer using immunoblot over immunoprecipitation, due to its practicality and lower cost. Notably, blotting-based assays were reported to have reduced specificity at detecting certain MSA/MAA subgroups. Description/Method A total of 472 JDM patients recruited via UK Juvenile Dermatomyositis Cohort and Biomarker Study (JDCBS) were included in this study. For immunoprecipitation cohort, the sera of 383 JDM-diagnosed patients were determined at the University of Bath using radio-labelled protein immunoprecipitation, and 140kDa bands were confirmed with ELISA for NXP2 or MDA5. For immunoblot cohort (n = 89), MSA/MAA results were obtained from the patients’ records at the centre of care. The immunoprecipitation group and immunoblot group were investigated for the frequency of each autoantibody subgroup within each cohort. The objective was to determine the sensitivity of each assay in detecting myositis relevant antibodies (MSA/MAA) in the context of JDM. Discussion/Results Overall, the majority of patients were female, and self-identified as white. Specifically, in immunoprecipitation cohort, 70.9% of the patients were female, while 77.1% of the patients self-identified as white. In the immunoblot cohort, 72.7% of the patient were female, while 65.9% self-identified as white. Regarding MSA/MAA status in each cohort, 225 out of 383 (58%) immunoprecipitation samples were positive for at least 1 myositis relevant autoantibody (MSA/MAA). In the immunoblot cohort the proportion was 53% (47 out of 89 samples). Despite the similar gender and ethnicity distribution, the frequencies of autoantibody subgroups varied between two cohorts. In descending order, the 3 most common MSAs detected by immunoprecipitation group were anti-TIF1γ (18.1%), anti-NXP2 (15.8%) and anti-MDA5 (5.9%). On the contrary, anti-MDA5 (15.5%) was the most prevalent autoantibody detected by immunoblot, followed by anti-TIF1γ (11.3%) and anti-NXP2 (9.3%), respectively. The prevalence of more than one myositis relevant autoantibodies detected in a patient was rare in both cohorts. Specifically, when excluding anti-Ro52, a MAA that is not detected with immunoprecipitation, 2.2% of the total patients in immunoblot cohort had more than 1 MSA/MAA. This rate is lower in immunoprecipitation cohort, as only 0.5% of the patients in this cohort were determined to be positive for more than one autoantibody subgroup. When accounting for anti-Ro52 in immunoblot cohort, 7 out of 8 anti-Ro52 positive patients were also positive for anti-MDA5, making up 7.9% of immunoblot cohort. Key learning points/Conclusion The variance between autoantibody frequencies detected by each method suggested that immunoprecipitation and immunoblot assays do not perform equally for all MSA and MAA. The lower detection of anti-TIF1γ in immunoblot is consistent with previous reports. Additionally, a potential reduction of sensitivity in anti-NXP2 detection using immunoblot is observed for the first time. Higher rate of anti-MDA5 in immunoblot cohort might reflect the earlier pre-treatment samples compared to the samples tested in immunoprecipitation cohort, as the titre of anti-MDA5 was reported to decrease with treatment. As MSA/MAA status are interpreted by clinicians to classify JDM patients into homogenous subgroups for more focused treatment plans, the reliability of autoantibody screening process is an issue of interest. Further investigations are necessary to characterise the sensitivity and specificity of each method.
Published: 2022

28. Biological classification of childhood arthritis: roadmap to a molecular nomenclature

Author: V. Michael Holers, Nicolino Ruperto, Rae S. M. Yeung, Alberto Martini, Robert A. Colbert, Peter A. Nigrovic, Seza Ozen, Lucy R. Wedderburn, and Susan D. Thompson
Subjects: 030203 arthritis & rheumatology, 0301 basic medicine, Childhood arthritis, business.industry, Inflammatory arthritis, Disease classification, Arthritis, Biological classification, medicine.disease, Bioinformatics, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Rheumatology, Genetic similarity, medicine, Biological evidence, business, Nomenclature
Abstract: Chronic inflammatory arthritis in childhood is heterogeneous in presentation and course. Most forms exhibit clinical and genetic similarity to arthritis of adult onset, although at least one phenotype might be restricted to children. Nevertheless, paediatric and adult rheumatologists have historically addressed disease classification separately, yielding a juvenile idiopathic arthritis (JIA) nomenclature that exhibits no terminological overlap with adult-onset arthritis. Accumulating clinical, genetic and mechanistic data reveal the critical limitations of this strategy, necessitating a new approach to defining biological categories within JIA. In this Review, we provide an overview of the current evidence for biological subgroups of arthritis in children, delineate forms that seem contiguous with adult-onset arthritis, and consider integrative genetic and bioinformatic strategies to identify discrete entities within inflammatory arthritis across all ages. Childhood-onset arthritis has historically been treated as a separate entity to adult-onset arthritis, with its own nomenclature and classification system. Biological evidence has revealed the limitations of the current approach, necessitating a fresh look at the classification of paediatric arthritis.
Published: 2021

29. Preexisting and de novo humoral immunity to SARS-CoV-2 in humans

Author: Dhira Joshi, Lucy R. Marshall, Lucy R. Wedderburn, Stavroula Paraskevopoulou, Steve Gamblin, Georgina H. Cornish, Sonia Gandhi, Charles Swanton, John W. McCauley, William Bolland, Svend Kjaer, Nikhil Faulkner, Hannah Rickman, Rachel Ulferts, Philip Hobson, D.J. Benton, Laura E. McCoy, Ana Agua-Doce, Rupert Beale, Annachiara Rosa, Chloe Roustan, Nicola O’Reilly, Catherine F Houlihan, Christopher Earl, Eleni Nastouli, A.G. Wrobel, Rachael Thompson, Brigitta Stockinger, Kirsty Thomson, Catherine Moore, Bethany R. Jebson, Anna Radziszewska, Coziana Ciurtin, Andrew Riddell, Saira Hussain, Emilie Sanchez, Peter Cherepanov, Elizabeth C. Rosser, Meredyth G. Ll Wilkinson, Kevin W. Ng, Ruth Harvey, Philip A. Walker, Hannah Peckham, Judith Heaney, Gee Yen Shin, Moira J. Spyer, and George Kassiotis
Subjects: Male, 0301 basic medicine, viruses, Antibodies, Viral, Viral Zoonoses, Immunoglobulin G, 0302 clinical medicine, 030212 general & internal medicine, skin and connective tissue diseases, Aged, 80 and over, chemistry.chemical_classification, Multidisciplinary, biology, medicine.diagnostic_test, virus diseases, Microbio, Middle Aged, Multidisciplinary Sciences, Titer, Spike Glycoprotein, Coronavirus, Science & Technology - Other Topics, Female, Antibody, Adult, General Science & Technology, Immunology, Flow cytometry, Young Adult, 03 medical and health sciences, Immunity, Report, medicine, Animals, Humans, Amino Acid Sequence, Aged, Science & Technology, SARS-CoV-2, fungi, COVID-19, biochemical phenomena, metabolism, and nutrition, Immunity, Humoral, Immunoglobulin A, body regions, HEK293 Cells, 030104 developmental biology, Epitope mapping, Immunoglobulin M, chemistry, Humoral immunity, biology.protein, Glycoprotein, Epitope Mapping, Reports
Abstract: Antibodies predating infection Immunological memory after infection with seasonal human coronaviruses (hCoVs) may potentially contribute to cross-protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Ng et al. report that in a cohort of 350 SARS-CoV-2–uninfected individuals, a small proportion had circulating immunoglobulin G (IgG) antibodies that could cross-react with the S2 subunit of the SARS-CoV-2 spike protein (see the Perspective by Guthmiller and Wilson). By contrast, COVID-19 patients generated IgA, IgG, and IgM antibodies that recognized both the S1 and S2 subunits. The anti-S2 antibodies from SARS-CoV-2–uninfected patients showed specific neutralizing activity against both SARS-CoV-2 and SARS-CoV-2 S pseudotypes. A much higher percentage of SARS-CoV-2–uninfected children and adolescents were positive for these antibodies compared with adults. This pattern may be due to the fact that children and adolescents generally have higher hCoV infection rates and a more diverse antibody repertoire, which may explain the age distribution of COVID-19 susceptibility. Science, this issue p. 1339; see also p. 1272, SARS-CoV-2 neutralizing antibodies can be found in some uninfected individuals—predominantly children and adolescents., Zoonotic introduction of novel coronaviruses may encounter preexisting immunity in humans. Using diverse assays for antibodies recognizing SARS-CoV-2 proteins, we detected preexisting humoral immunity. SARS-CoV-2 spike glycoprotein (S)–reactive antibodies were detectable using a flow cytometry–based method in SARS-CoV-2–uninfected individuals and were particularly prevalent in children and adolescents. They were predominantly of the immunoglobulin G (IgG) class and targeted the S2 subunit. By contrast, SARS-CoV-2 infection induced higher titers of SARS-CoV-2 S–reactive IgG antibodies targeting both the S1 and S2 subunits, and concomitant IgM and IgA antibodies, lasting throughout the observation period. SARS-CoV-2–uninfected donor sera exhibited specific neutralizing activity against SARS-CoV-2 and SARS-CoV-2 S pseudotypes. Distinguishing preexisting and de novo immunity will be critical for our understanding of susceptibility to and the natural course of SARS-CoV-2 infection.
Published: 2020

30. Identification and prediction of novel classes of long-term disease trajectories for patients with juvenile dermatomyositis using growth mixture models

Author: Charalampia Papadopoulou, Muthana Al-Obaidi, Lucy R. Wedderburn, Bianca De Stavola, Liza J McCann, Sarah L Tansley, Neil Martin, Neil McHugh, Sandrine Compeyrot-Lacassagne, Claire T Deakin, and Clarissa Pilkington
Subjects: Male, medicine.medical_specialty, Time Factors, biostatistics, patient outcomes, Disease, JDM, Dermatomyositis, paediatric rheumatology, Rheumatology, Lasso regression, Internal medicine, medicine, Humans, Pharmacology (medical), Child, Juvenile dermatomyositis, AcademicSubjects/MED00360, Skin, Models, Statistical, business.industry, Odds ratio, Clinical Science, Mixture model, medicine.disease, United Kingdom, Child, Preschool, Disease Progression, Female, Biostatistics, Lipodystrophy, business, myositis
Abstract: Objectives Uncertainty around clinical heterogeneity and outcomes for patients with JDM represents a major burden of disease and a challenge for clinical management. We sought to identify novel classes of patients having similar temporal patterns in disease activity and relate them to baseline clinical features. Methods Data were obtained for n = 519 patients, including baseline demographic and clinical features, baseline and follow-up records of physician’s global assessment of disease (PGA), and skin disease activity (modified DAS). Growth mixture models (GMMs) were fitted to identify classes of patients with similar trajectories of these variables. Baseline predictors of class membership were identified using Lasso regression. Results GMM analysis of PGA identified two classes of patients. Patients in class 1 (89%) tended to improve, while patients in class 2 (11%) had more persistent disease. Lasso regression identified abnormal respiration, lipodystrophy and time since diagnosis as baseline predictors of class 2 membership, with estimated odds ratios, controlling for the other two variables, of 1.91 for presence of abnormal respiration, 1.92 for lipodystrophy and 1.32 for time since diagnosis. GMM analysis of modified DAS identified three classes of patients. Patients in classes 1 (16%) and 2 (12%) had higher levels of modified DAS at diagnosis that improved or remained high, respectively. Patients in class 3 (72%) began with lower DAS levels that improved more quickly. Higher proportions of patients in PGA class 2 were in DAS class 2 (19%, compared with 16 and 10%). Conclusion GMM analysis identified novel JDM phenotypes based on longitudinal PGA and modified DAS.
Published: 2020

31. P222 Clinical features of extra-muscular disease in dermatomyositis and anti-synthetase syndrome patients with skin involvement classified by presence of disease-specific autoantibodies: results from the EuroMyositis registry

Author: Ryan M Hum, James B Lilleker, Janine A Lamb, William E Ollier, Guochung Wang, Lucy R Wedderburn, Louise P Diederichsen, Jens Schmidt, Paula Oakley, Olivier Benveniste, Maria G Danieli, Katalin Danko, Nguyen T. P Thuy, Monica V. D Mercado, Helena Andersson, Boel D Paepe, Jan L. D Bleecker, Britta Maurer, Liza J McCann, Nicolo Pipitone, Neil McHugh, Paul New, Jiri Vencovsky, Ingrid E Lundberg, and Hector Chinoy
Subjects: Rheumatology, Pharmacology (medical)
Abstract: Background/Aims Anti-synthetase syndrome (ASS) represents a distinct entity within myositis spectrum disorders; however, correct classification of patients with anti-tRNA synthetase autoantibodies and skin manifestations akin to dermatomyositis (DM) remains uncertain. Our aim was to compare clinical characteristics, skin involvement, and malignancy, between patients with ASS and DM, classified by disease-specific autoantibodies. Methods Data from 05/2009-03/2016 from 9 countries from the prospective, myositis EuroMyositis registry were downloaded. Those with anti-tRNA synthetase autoantibodies (Jo-1/PL-7/PL-12/OJ/EJ/KS) were classified as ASS, and those with Mi-2/TIF1-γ/NXP2/SAE/MDA5 autoantibodies as DM. Clinical phenotypes including malignancies (except skin malignancies) were tabulated. Characteristics of patients with skin involvement (excluding mechanic’s hands and Raynaud’s phenomenon) were compared using Fisher’s exact test with Bonferroni corrected p-values. Results Of 3,067 patients, 2,028 had autoantibody profiling results (66.1%), of which 783 (38.6%) were positive for at least one of the autoantibodies being considered. Five patients with dual autoantibody specificities were excluded. Of the remaining 778, 320 (41.1%) were classified as DM, and 458 (58.9%) as ASS. Median age at diagnosis was 48.2 years (interquartile range [IQR] 37.5 to 57.8) in the DM cohort and 49 (IQR 38.3 to 62.2) in the ASS cohort. Skin involvement was present in 277 (86.6%) DM patients (DM skin) vs 204 (44.5%) ASS patients (ASS skin) (pcorr Conclusion Patients with ASS have frequent skin involvement but also a distinct clinical phenotype compared to DM. These findings may inform the development of future classification criteria for ASS. Disclosure R.M. Hum: None. J.B. Lilleker: None. J.A. Lamb: None. W.E. Ollier: None. G. Wang: None. L.R. Wedderburn: None. L.P. Diederichsen: None. J. Schmidt: None. P. Oakley: None. O. Benveniste: None. M.G. Danieli: None. K. Danko: None. N.T.P. Thuy: None. M.V.D. Mercado: None. H. Andersson: None. B.D. Paepe: None. J.L.D. Bleecker: None. B. Maurer: None. L.J. McCann: None. N. Pipitone: None. N. McHugh: None. P. New: None. J. Vencovsky: None. I.E. Lundberg: None. H. Chinoy: None.
Published: 2022

32. OA19 Successes and challenges in harmonising four national juvenile idiopathic arthritis cohorts: an example from CLUSTER consortium

Author: Saskia Lawson-Tovey, Lucy R Wedderburn, Nophar Geifman, Michael Barnes, and Kimme L Hyrich
Subjects: Rheumatology, Pharmacology (medical)
Abstract: Background/Aims The CLUSTER consortium aims to identify biomarkers and strata that improve personalised treatments for JIA/JIA-uveitis. By bringing together knowledge and data, CLUSTER can conduct novel analyses in this rare, heterogeneous disease. Data harmonisation across existing JIA cohorts facilitates new, larger datasets that would otherwise take years to collect; however, challenges exist as datasets are often collected autonomously. Here we present progress towards a large-scale, unique JIA data resource, bringing together treatment data from four real-world JIA treatment studies. Methods Four studies (CAPS, CHARMS, BCRD and BSPAR-ETN; the latter two being part of the UK JIA Biologics register) contributed data into CLUSTER. We created two clinical datasets of JIA patients starting first-line methotrexate (MTX) or tumour necrosis factor inhibitors (TNFi). Variables were selected based on a previously developed core dataset, accounting for different levels of granularity across studies. The same inclusion and exclusion criteria were agreed for both datasets, designed to allow for combined analysis of these. OpenPseudonymiser software encrypted NHS numbers - these were matched cross-study to identify duplicates and checked against known duplicate lists. Errors in NHS numbers and existing duplicate matches were identified and corrected. Each NHS number was assigned a CLUSTER ID, meaning one child has the same ID across all relevant studies such that children contributing similar data across multiple studies could be identified. Results A total of 7013 records (from 5435 individuals) were identified, of which 2882 (41%, corresponding to 1304 individuals) represented the same child across >1 study. 197 individuals had duplicate records within one study, 961 in two studies, 142 in three, and four children had duplicate records in all four studies. After removing 350 MTX and 605 TNFi duplicate entries, the final datasets contain 2899 and 2401 unique MTX and TNFi patients respectively; 1018 are in both datasets having received both treatments. Missingness across core outcome variables ranged from 10% (active joint count MTX timepoint 2) to 60% (physician VAS TNFi timepoint 2) and was not improved through combining datasets with duplicate entries. Specificity in some variables was lost to allow integration by combining data using least common denominators (e.g. ethnicity captured as Caucasian/Non-Caucasian, despite more specific categories available in some studies). Conclusion Combining data across studies has achieved dataset sizes rarely seen in JIA, which is invaluable to progressing research into personalised treatments and disease outcomes. However, losing specificity in some variables and missingness (a known challenge in observational data) and their impact on future analyses requires further consideration. Ongoing work includes identifying patients with both clinical and biological data that can be combined for more in-depth analyses. Both datasets are available for researchers to use via the CLUSTER Consortium Data Management Committee. Disclosure S. Lawson-Tovey: None. L.R. Wedderburn: Consultancies; L.W. reports consulting fees from Pfizer unrelated to this work. Grants/research support; CLUSTER consortium receives support from AbbVie, UCB, Pfizer, Sobi and GSK. N. Geifman: None. M. Barnes: None. K.L. Hyrich: Grants/research support; KLH reports grant income from BMS, UCB, and Pfizer. Other; KLH reports non-personal speaker's fees from Abbvie.
Published: 2022

33. Use of MRP8/14 in clinical practice as a predictor of outcome after methotrexate withdrawal in patients with juvenile idiopathic arthritis

Author: Emma J. Sumner, Beverley Almeida, Jason Palman, Peter Bale, Clare Heard, Dirk Holzinger, Johannes Roth, Dirk Foell, Emily Robinson, Simona Ursu, Chris Wallace, Kimberly Gilmour, Lucy R. Wedderburn, Elizabeth Ralph, Wallace, Chris [0000-0001-9755-1703], and Apollo - University of Cambridge Repository
Subjects: Methotrexate, Treatment Outcome, Rheumatology, Antirheumatic Agents, Medizin, Humans, General Medicine, Symptom Flare Up, skin and connective tissue diseases, Arthritis, Juvenile, Biomarkers
Abstract: The objective of this study was to determine the effectiveness of MRP8/14 as a predictor of disease flare in patients with juvenile idiopathic arthritis (JIA) following the withdrawal of methotrexate (MTX) in a routine clinical setting. All MRP8/14 tests performed at a single centre in a 27-month period were considered for analysis. Patients were assessed against criteria for inactive disease and subsequent disease flare. Decisions on whether or not to stop treatment were recorded. MRP8/14 results were assessed in conjunction with clinical information. Clinicians were also surveyed to investigate if MRP8/14 influenced their decision to discontinue MTX where this was available at that time point. One hundred four cases met the inclusion criteria during the study period. Although there was no significant difference in flares between patients with an elevated or low MRP8/14 value, in those who stopped MTX (n = 22), no patients with a low MRP8/14 (≤ 4000 ng/ml) result flared (follow-up time 12 months). Clinicians reported that for patients with clinically inactive disease and an elevated MRP8/14 result (> 4000 ng/ml), none would advise withdrawal of MTX. Low MRP8/14 was interpreted favourably when considering stopping MTX treatment in patients with JIA. Implementation of MRP8/14 testing has changed clinical practice at this centre. However, the observation that some patients in our cohort who had an elevated MRP8/14 value did not flare after stopping MTX for non-disease-related reasons highlights the need for further biomarkers to predict the risk of flare off medication in JIA and aid clinicians in treatment decisions. Key Points• First study of serum MRP8/14 measurement in clinical practice to inform treatment decisions in patients with JIA.• No patients with a low MRP8/14 test result went on to suffer a disease flare in 12 months of follow follow-up.• Further biomarkers are needed to predict the risk of flare off medication in JIA and treatment decisions.
Published: 2022

34. You give me a name that I can’t say, but I have to explain what it is every day: the power of poetry to share stories from young people with a rare disease

Author: Faith Gibson, Lucy R. Wedderburn, and P. Livermore
Subjects: 030506 rehabilitation, Poetry, Notice, Serendipity, media_common.quotation_subject, 05 social sciences, Rehabilitation, Media studies, 050401 social sciences methods, Silence, Phenomenology (philosophy), 03 medical and health sciences, Clinical Psychology, Presentation, 0504 sociology, Feeling, Sociology, 0305 other medical science, Qualitative research, media_common
Abstract: Qualitative research is about people’s lives; their stories, their thoughts, their feelings, and their experiences. Researchers continue to reflect on the best way to present other people’s stories in a way that stays true to their accounts and delivers the message in a manner which resonates. This article presents one such way, discovered through serendipity, which allowed the researcher to share findings from young people’s stories eloquently and passionately to audiences of healthcare professionals from different disciplines. The silence and raw emotion witnessed after the poetry delivery was akin to that often seen during childbirth when those around are stunned into thoughtful awe. The poetry, which was crafted entirely from young participant’s interview transcripts had two benefits; 1) sharing young people’s stories using their own words and 2) using a presentation format that demanded attention; so that people took notice, listened and reflected on the words and experiences being expressed.
Published: 2019

35. Towards molecular-pathology informed clinical trials in childhood arthritis to achieve precision medicine in juvenile idiopathic arthritis

Author: Lucy R Wedderburn, Athimalaipet V Ramanan, Adam P Croft, Kimme L Hyrich, and Andrew D Dick
Subjects: Clinical trials, Synovial biology, Rheumatology, Precision medicine, Immunology, Pathology, Immunology and Allergy, Juvenile idiopathic arthritis, Stratification, General Biochemistry, Genetics and Molecular Biology
Abstract: In childhood arthritis, collectively known as Juvenile idiopathic arthritis (JIA), the rapid rise of available licensed biological and targeted small molecule treatments in recent years has led to improved outcomes. However, real-world data from multiple countries and registries show that despite a large number of available drugs, many children and young people continue to suffer flares and experience significant periods of time with active disease for many years. More than 50% of young people with JIA require ongoing immune suppression well into adult life, and they may have to try multiple different treatments in that time. There are currently no validated tools with which to select specific treatments, nor biomarkers of response to assist in such choices, therefore, current management uses essentially a trial-and-error approach. A further consequence of recent progress is a reducing pool of available children or young people who are eligible for new trials. In this review we consider how progress towards a molecular based approach to defining treatment targets and informing trial design in JIA, combined with novel approaches to clinical trials, could provide strategies to maximise discovery and progress, in order to move towards precision medicine for children with arthritis.
Published: 2022

36. Mapping the current psychology provision for children and young people with juvenile dermatomyositis

Author: Suzanne Gray, Lucy R. Wedderburn, Polly Livermore, Liza J McCann, Kathleen Mulligan, and Faith Gibson
Subjects: psychosocial, medicine.medical_specialty, Emotional support, RJ101, psychology provision, BF, nurse support, RT, paediatric rheumatology, Rheumatology, Internal medicine, Health care, medicine, Juvenile dermatomyositis, Service (business), business.industry, juvenile dermatomyositis, medicine.disease, Family medicine, Original Article, Autoimmune condition, business, Psychology, AcademicSubjects/MED00010, Psychosocial, Paediatric rheumatology
Abstract: Objectives Juvenile Dermatomyositis (JDM) is a rare, chronic autoimmune condition of childhood, with known psychosocial implications. In this study, we sought to establish current psychological support for children and young people across the UK with rheumatic conditions, with a specific focus on those with JDM. Methods Electronic surveys were distributed to the 15 centres that belong to the JDM Research Group in the UK, collecting responses from health-care professionals in the fields of medicine, nursing and psychology. Results One hundred per cent of professionals from medicine and nursing replied from all 15 centres. Of these, 7 (47%) did not have a named psychologist as part of their rheumatology team, despite the majority [13 (87%)] having >200 paediatric rheumatology patients. Of the remaining centres, hospital psychology provision varied considerably. When rating their service, only 3 (8%) of 40 professionals scored their service as five (where one is poor and five is excellent); there were wide discrepancies in these scores. Many challenges were discussed, including limited psychology provision, lack of time and difficulties in offering support across large geographical areas. Conclusion Many of the challenges discussed are applicable to other centres worldwide. Suggestions have been proposed that might help to improve the situation for children and young people with rheumatic conditions, including JDM. Based on these findings, we suggest that rheumatology teams maximize use of these data to advocate and work toward more comprehensive psychology provision and support in their individual centres.
Published: 2021

37. Innate Lymphoid Cells and T Cells Contribute to the Interleukin‐17A Signature Detected in the Synovial Fluid of Patients With Juvenile Idiopathic Arthritis

Author: Mona Bajaj-Elliott, Lucy R. Wedderburn, Chantal L. Duurland, David Bending, Hannah Lom, and Elizabeth C. Rosser
Subjects: CD4-Positive T-Lymphocytes, Male, 0301 basic medicine, Adolescent, medicine.medical_treatment, Immunology, Arthritis, Peripheral blood mononuclear cell, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, T-Lymphocyte Subsets, Synovial Fluid, Humans, Immunology and Allergy, Medicine, Synovial fluid, Lymphocytes, Child, skin and connective tissue diseases, Natural Cytotoxicity Triggering Receptor 2, business.industry, Brief Report, Interleukin-17, Innate lymphoid cell, Pediatric Rheumatology, medicine.disease, Arthritis, Juvenile, Immunity, Innate, 030104 developmental biology, Cytokine, 030220 oncology & carcinogenesis, Leukocytes, Mononuclear, Cytokines, Female, Interleukin 17, IL17A, business, CD8
Abstract: Objective Evidence suggests that aberrant function of innate lymphoid cells (ILCs), whose functional and transcriptional profiles overlap with those of Th cell subsets, contributes to immune‐mediated pathologies. To date, analysis of juvenile idiopathic arthritis (JIA) immune pathology has concentrated on the contribution of CD4+ T cells; we have previously identified an expansion of Th17 cells within the synovial fluid (SF) of JIA patients. We undertook this study to extend this analysis to further investigate the role of ILCs and other interleukin‐17 (IL‐17)–producing T cell subsets in JIA. Methods ILCs and CD3+ T cell subsets were defined in peripheral blood mononuclear cells (PBMCs) from healthy adults, healthy children, and JIA patients and in SF mononuclear cells (SFMCs) from JIA patients using flow cytometry. Defined subsets in SFMCs were correlated with clinical measures including physician's global assessment of disease activity on a visual analog scale, number of joints with active disease, and erythrocyte sedimentation rate. Transcription factor and cytokine profiles of sorted ILCs were assessed by quantitative reverse transcriptase–polymerase chain reaction. Results Group 1 ILCs (ILC1s), NKp44− group 3 ILCs (natural cytotoxicity receptor–negative [NCR−] ILC3s), and NKp44+ ILC3s (NCR+ ILC3s) were enriched in JIA SFMCs compared to PBMCs, which corresponded to an increase in transcripts for TBX21, IFNG, and IL17A. Of the ILC subsets, the frequency of NCR− ILC3s in JIA SFMCs displayed the strongest positive association with clinical measures, which was mirrored by an expansion in IL‐17A+CD4+, IL‐17A+CD8+, and IL‐17A+ γδ T cells. Conclusion We demonstrate that the strength of the IL‐17A signature in JIA SFMCs is determined by multiple lymphoid cell types, including NCR− ILC3s and IL‐17A+CD4+, IL‐17A+CD8+, and IL‐17A+ γδ T cells. These observations may have important implications for the development of stratified therapeutics.
Published: 2019

38. A novel dried blood spot-LCMS method for the quantification of methotrexate polyglutamates as a potential marker for methotrexate use in children.

Author: Ahmed F Hawwa, Abdelqader Albawab, Madeleine Rooney, Lucy R Wedderburn, Michael W Beresford, and James C McElnay
Subjects: Medicine, Science
Abstract: Development and validation of a selective and sensitive LCMS method for the determination of methotrexate polyglutamates in dried blood spots (DBS).DBS samples [spiked or patient samples] were prepared by applying blood to Guthrie cards which was then dried at room temperature. The method utilised 6-mm disks punched from the DBS samples (equivalent to approximately 12 µl of whole blood). The simple treatment procedure was based on protein precipitation using perchloric acid followed by solid phase extraction using MAX cartridges. The extracted sample was chromatographed using a reversed phase system involving an Atlantis T3-C18 column (3 µm, 2.1 × 150 mm) preceded by Atlantis guard column of matching chemistry. Analytes were subjected to LCMS analysis using positive electrospray ionization.The method was linear over the range 5-400 nmol/L. The limits of detection and quantification were 1.6 and 5 nmol/L for individual polyglutamates and 1.5 and 4.5 nmol/L for total polyglutamates, respectively. The method has been applied successfully to the determination of DBS finger-prick samples from 47 paediatric patients and results confirmed with concentrations measured in matched RBC samples using conventional HPLC-UV technique.The methodology has a potential for application in a range of clinical studies (e.g. pharmacokinetic evaluations or medication adherence assessment) since it is minimally invasive and easy to perform, potentially allowing parents to take blood samples at home. The feasibility of using DBS sampling can be of major value for future clinical trials or clinical care in paediatric rheumatology.
Published: 2014
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39. Increased presence of FOXP3+ regulatory T cells in inflamed muscle of patients with active juvenile dermatomyositis compared to peripheral blood.

Author: Yvonne Vercoulen, Felicitas Bellutti Enders, Jenny Meerding, Maud Plantinga, Elisabeth F Elst, Hemlata Varsani, Christa van Schieveen, Mette H Bakker, Mark Klein, Rianne C Scholman, Wim Spliet, Valeria Ricotti, Hans J P M Koenen, Roel A de Weger, Lucy R Wedderburn, Annet van Royen-Kerkhof, and Berent J Prakken
Subjects: Medicine, Science
Abstract: Juvenile dermatomyositis (JDM) is an immune-mediated inflammatory disease affecting the microvasculature of skin and muscle. CD4+ CD25+ FOXP3+ regulatory T cells (Tregs) are key regulators of immune homeostasis. A role for Tregs in JDM pathogenesis has not yet been established. Here, we explored Treg presence and function in peripheral blood and muscle of JDM patients. We analyzed number, phenotype and function of Tregs in blood from JDM patients by flow cytometry and in vitro suppression assays, in comparison to healthy controls and disease controls (Duchenne's Muscular Dystrophy). Presence of Tregs in muscle was analyzed by immunohistochemistry. Overall, Treg percentages in peripheral blood of JDM patients were similar compared to both control groups. Muscle biopsies of new onset JDM patients showed increased infiltration of numbers of T cells compared to Duchenne's muscular dystrophy. Both in JDM and Duchenne's muscular dystrophy the proportion of FOXP3+ T cells in muscles were increased compared to JDM peripheral blood. Interestingly, JDM is not a self-remitting disease, suggesting that the high proportion of Tregs in inflamed muscle do not suppress inflammation. In line with this, peripheral blood Tregs of active JDM patients were less capable of suppressing effector T cell activation in vitro, compared to Tregs of JDM in clinical remission. These data show a functional impairment of Tregs in a proportion of patients with active disease, and suggest a regulatory role for Tregs in JDM inflammation.
Published: 2014
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40. Juvenile dermatomyositis: novel treatment approaches and outcomes

Author: Clarissa Pilkington, Lucy R. Wedderburn, and Giulia C. Varnier
Subjects: 030203 arthritis & rheumatology, medicine.medical_specialty, International studies, business.industry, Biopsy, Outcome measures, medicine.disease, Dermatomyositis, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Outcome Assessment, Health Care, medicine, Humans, Immunologic Factors, 030212 general & internal medicine, Muscle, Skeletal, Rituximab, Intensive care medicine, business, Glucocorticoids, Juvenile dermatomyositis
Abstract: The aim of this article is to provide a summary of the recent therapeutic advances and the latest research on outcome measures for juvenile dermatomyositis (JDM).Several new international studies have developed consensus-based guidelines on diagnosis, outcome measures and treatment of JDM to standardize and improve patient care. Myositis-specific antibodies together with muscle biopsy histopathology may help the clinician to predict disease outcome. A newly developed MRI-based scoring system has been developed to standardize the use of MRI in assessing disease activity in JDM. New data regarding the efficacy and safety of rituximab, especially for skin disease, and cyclophosphamide in JDM support the use of these medications for severe refractory cases.International network studies, new biomarkers and outcome measures have led to significant progress in understanding and managing the rare inflammatory myositis conditions such as JDM.
Published: 2018

41. Biological classification of childhood arthritis: roadmap to a molecular nomenclature

Author: Peter A, Nigrovic, Robert A, Colbert, V Michael, Holers, Seza, Ozen, Nicolino, Ruperto, Susan D, Thompson, Lucy R, Wedderburn, Rae S M, Yeung, and Alberto, Martini
Subjects: Phenotype, Terminology as Topic, Computational Biology, Humans, Child, Polymorphism, Single Nucleotide, Arthritis, Juvenile
Abstract: Chronic inflammatory arthritis in childhood is heterogeneous in presentation and course. Most forms exhibit clinical and genetic similarity to arthritis of adult onset, although at least one phenotype might be restricted to children. Nevertheless, paediatric and adult rheumatologists have historically addressed disease classification separately, yielding a juvenile idiopathic arthritis (JIA) nomenclature that exhibits no terminological overlap with adult-onset arthritis. Accumulating clinical, genetic and mechanistic data reveal the critical limitations of this strategy, necessitating a new approach to defining biological categories within JIA. In this Review, we provide an overview of the current evidence for biological subgroups of arthritis in children, delineate forms that seem contiguous with adult-onset arthritis, and consider integrative genetic and bioinformatic strategies to identify discrete entities within inflammatory arthritis across all ages.
Published: 2021

42. A survey to understand the feelings towards and impact of COVID-19 on the households of juvenile dermato myositis patients from a parent or carer perspective

Author: Kathryn O’Brien, Wing Li Wu, Meredyth Grace Llewellyn Wilkinson, Lucy R. Wedderburn, Claire T Deakin, and Polly Livermore
Subjects: sources, medicine.medical_specialty, Concise Report, media_common.quotation_subject, JDM, information, Rheumatology, Pandemic, medicine, Juvenile, Juvenile dermatomyositis, media_common, juvenile dermatomyositis, business.industry, Perspective (graphical), COVID-19, medicine.disease, Feeling, Family medicine, Cohort, impact, Anxiety, medication, feelings, Worry, medicine.symptom, AcademicSubjects/MED00010, business
Abstract: Objectives This aim of this study was to gain a better understanding of how parents and carers feel about the effects and impact of the coronavirus disease 2019 (COVID-19) pandemic lockdown and how this impacted upon their child/young person with JDM. Method We approached 139 participants from the JDM Cohort Biomarker Study (JDCBS), with specific consent to approach electronically for research studies. A secure electronic questionnaire with study introduction was sent to participants for their parents and carers around the UK to complete. It consisted of 20 questions about the impact of the pandemic on their child or young person’s clinical care. Data were analysed quantitatively and qualitatively. Results There were 76 (55%) responses to the survey. More than 50% of participants were actively being treated for their JDM at the point of survey completion as recorded by their parent or carer. More than 40% attested to disrupted treatment owing to COVID-19. The biggest impact upon clinical care was cancellation of appointments, initiating virtual appointments and extension of time between blood tests. Parents and carers expressed their own feelings of worry, concern and anxiety, but also those of their child or young person. Conclusion Families who have a child or young person with JDM have been affected by COVID-19. Qualitative comments highlight that it has been a very difficult time. Further investigation is required into this area and could be compared with research on the effects of COVID-19 on other patient groups with chronic disease.
Published: 2021

43. Anti-Cytosolic 5'-Nucleotidase 1A Autoantibodies Are Absent in Juvenile Dermatomyositis

Author: Wilma Vree Egberts, Eline A. Visser, Ger J. M. Pruijn, Wolfgang Schlumberger, Annet van Royen-Kerkhof, Baziel G.M. van Engelen, Lucy R. Wedderburn, Christiaan G J Saris, Judith Wienke, Anke Rietveld, Sarah L Tansley, and Hui Lu
Subjects: 030203 arthritis & rheumatology, business.industry, Immunology, Case-control study, Autoantibody, Bio-Molecular Chemistry, medicine.disease, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], 5'-nucleotidase, 03 medical and health sciences, Cytosol, 0302 clinical medicine, Rheumatology, Nucleotidase, Cohort, medicine, Immunology and Allergy, Juvenile, business, 030217 neurology & neurosurgery, Juvenile dermatomyositis
Abstract: Contains fulltext : 238504.pdf (Publisher’s version ) (Open Access) OBJECTIVE: To assess anti-cytosolic 5'-nucleotidase 1A (anti-cN-1A) autoantibodies in children with juvenile dermatomyositis (DM) and healthy controls, using 3 different methods of antibody detection, as well as verification of the results in an independent cohort. METHODS: Anti-cN-1A reactivity was assessed in 34 Dutch juvenile DM patients and 20 healthy juvenile controls using the following methods: a commercially available full-length cN-1A enzyme-linked immunosorbent assay (ELISA), a synthetic peptide ELISA, and immunoblotting with a lysate from cN-1A-expressing HEK 293 cells. Sera from juvenile DM patients with active disease and those with disease in remission were analyzed. An independent British cohort of 110 juvenile DM patients and 43 healthy juvenile controls was assessed using an in-house full-length cN-1A ELISA. RESULTS: Anti-cN-1A reactivity was not present in sera from juvenile DM patients or healthy controls when tested with the commercially available full-length cN-1A ELISA or by immunoblotting, in either active disease or disease in remission. Additionally, in the British juvenile DM cohort, anti-cN-1A reactivity was not detected. Three Dutch juvenile DM patients had weakly positive results for 1 of 3 synthetic cN-1A peptides measured by ELISA. CONCLUSION: Juvenile DM patients and young healthy individuals did not show anti-cN-1A reactivity as assessed by different antibody detection techniques.
Published: 2021

44. Male sex identified by global COVID-19 meta-analysis as a risk factor for death and ITU admission

Author: Charles Raine, Claire T Deakin, Nina M. de Gruijter, Hannah Peckham, Kate Webb, Lucy R. Wedderburn, Elizabeth C. Rosser, Anna Radziszewska, and Coziana Ciurtin
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Epidemiology, Science, Systems analysis, General Physics and Astronomy, Disease, Article, General Biochemistry, Genetics and Molecular Biology, Odds, 03 medical and health sciences, 0302 clinical medicine, Sex Factors, Intensive care, medicine, Humans, 030212 general & internal medicine, Risk factor, Mortality, Pandemics, Anecdotal evidence, Uncategorized, Multidisciplinary, business.industry, SARS-CoV-2, Mortality rate, COVID-19, General Chemistry, Intensive Care Units, 030104 developmental biology, Risk factors, Viral infection, Meta-analysis, Female, business, Demography
Abstract: Anecdotal evidence suggests that Coronavirus disease 2019 (COVID-19), caused by the coronavirus SARS-CoV-2, exhibits differences in morbidity and mortality between sexes. Here, we present a meta-analysis of 3,111,714 reported global cases to demonstrate that, whilst there is no difference in the proportion of males and females with confirmed COVID-19, male patients have almost three times the odds of requiring intensive treatment unit (ITU) admission (OR = 2.84; 95% CI = 2.06, 3.92) and higher odds of death (OR = 1.39; 95% CI = 1.31, 1.47) compared to females. With few exceptions, the sex bias observed in COVID-19 is a worldwide phenomenon. An appreciation of how sex is influencing COVID-19 outcomes will have important implications for clinical management and mitigation strategies for this disease., Anecdotal reports suggest potential severity and outcome differences between sexes following infection by SARS-CoV-2. Here, the authors perform meta-analyses of more than 3 million cases collected from global public data to demonstrate that male patients with COVID-19 are 3 times more likely to require intensive care, and have ~40% higher death rate.
Published: 2020
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45. Patient-reported wellbeing and clinical disease measures over time captured by multivariate trajectories of disease activity in individuals with juvenile idiopathic arthritis in the UK: a multicentre prospective longitudinal study

Author: Joyce Davidson, Coziana Ciurtin, Wei-Yu Lin, Kimme L. Hyrich, Jenna F. Gritzfeld, Athimalaipet V Ramanan, Wendy Thomson, Elizabeth Ralph, Sally-Anne Dews, Aline Kimonyo, Fatjon Dekaj, Paul Martin, Emil Carlsson, Zoe Wanstall, Lucy R. Wedderburn, Saskia Lawson-Tovey, Annie Yarwood, Beth Jebson, Toby Kent, Stephanie J W Shoop-Worrall, Sandra Ng, Chris Wallace, Emily Robinson, Joanna Fairlie, Michael R. Barnes, Alice Chieng, Samantha L. Smith, Andrew D. Dick, Teresa Duerr, Damian Tarasek, Andrew D. Morris, Jessica Neisen, Melissa Kartawinata, Fatema Merali, Emma Sumner, Eileen Baildam, Helen Neale, Michael W. Beresford, Helen E. Foster, Soumya Raychaudhuri, Flora McErlane, Gavin Cleary, Gil Reynolds Diogo, Yiannis Ioannou, and Nophar Geifman
Subjects: Longitudinal study, Pediatrics, medicine.medical_specialty, Childhood arthritis, business.industry, Immunology, Arthritis, Articles, Disease, medicine.disease, Juvenile Arthritis Disease Activity Score, Rheumatology, medicine, Population study, Immunology and Allergy, Prospective cohort study, business, Socioeconomic status
Abstract: Summary Background Juvenile idiopathic arthritis (JIA) is a heterogeneous disease, the signs and symptoms of which can be summarised with use of composite disease activity measures, including the clinical Juvenile Arthritis Disease Activity Score (cJADAS). However, clusters of children and young people might experience different global patterns in their signs and symptoms of disease, which might run in parallel or diverge over time. We aimed to identify such clusters in the 3 years after a diagnosis of JIA. The identification of these clusters would allow for a greater understanding of disease progression in JIA, including how physician-reported and patient-reported outcomes relate to each other over the JIA disease course. Methods In this multicentre prospective longitudinal study, we included children and young people recruited before Jan 1, 2015, to the Childhood Arthritis Prospective Study (CAPS), a UK multicentre inception cohort. Participants without a cJADAS score were excluded. To assess groups of children and young people with similar disease patterns in active joint count, physician's global assessment, and patient or parental global evaluation, we used latent profile analysis at initial presentation to paediatric rheumatology and multivariate group-based trajectory models for the following 3 years. Optimal models were selected on the basis of a combination of model fit, clinical plausibility, and model parsimony. Finding Between Jan 1, 2001, and Dec 31, 2014, 1423 children and young people with JIA were recruited to CAPS, 239 of whom were excluded, resulting in a final study population of 1184 children and young people. We identified five clusters at baseline and six trajectory groups using longitudinal follow-up data. Disease course was not well predicted from clusters at baseline; however, in both cross-sectional and longitudinal analyses, substantial proportions of children and young people had high patient or parent global scores despite low or improving joint counts and physician global scores. Participants in these groups were older, and a higher proportion of them had enthesitis-related JIA and lower socioeconomic status, compared with those in other groups. Interpretation Almost one in four children and young people with JIA in our study reported persistent, high patient or parent global scores despite having low or improving active joint counts and physician's global scores. Distinct patient subgroups defined by disease manifestation or trajectories of progression could help to better personalise health-care services and treatment plans for individuals with JIA. Funding Medical Research Council, Versus Arthritis, Great Ormond Street Hospital Children's Charity, Olivia's Vision, and National Institute for Health Research.
Published: 2020

46. COVID-19 infection in children and adolescents

Author: Coziana Ciurtin, Lucy R. Wedderburn, and Meena Naja
Subjects: medicine.medical_specialty, Pediatrics, Adolescent, Pneumonia, Viral, Disease, Intensive Care Units, Pediatric, Real-Time Polymerase Chain Reaction, Asymptomatic, Antiviral Agents, 03 medical and health sciences, Betacoronavirus, 0302 clinical medicine, Extracorporeal Membrane Oxygenation, Adrenal Cortex Hormones, 030225 pediatrics, Epidemiology, medicine, Sore throat, Humans, 030212 general & internal medicine, Mortality, Child, Pandemics, business.industry, Transmission (medicine), SARS-CoV-2, Outbreak, COVID-19, General Medicine, medicine.disease, Systemic Inflammatory Response Syndrome, Systemic inflammatory response syndrome, Clinical trial, medicine.symptom, Hemofiltration, business, Coronavirus Infections
Abstract: The COVID-19 pandemic has predominantly affected the adult population. The disease is less well-defined in children (≤18 years). This review summarises the current understanding of the epidemiology, clinical manifestations, and management of COVID-19 in children and adolescents. The prevalence of COVID-19 is significantly lower in children than adults, but paediatric disease is likely underdiagnosed as a result of the high numbers of asymptomatic or mild cases. Children are vulnerable to family cluster outbreaks, but are unlikely to be index cases within a household. Vertical transmission or breast milk transmission are yet to be proven. Between 10 and 90% of paediatric COVID-19 cases are asymptomatic. Symptomatic cases typically present with mild symptoms, including cough, fever and sore throat. Intensive care admission and mortality are rare. Paediatric multisystem inflammatory syndrome temporally associated with COVID-19 is a rare, but severe, newly emerging phenotype. At present, there is no specific treatment for COVID-19 in adults or children; management is usually supportive. For severe or critical disease, including paediatric multisystem inflammatory syndrome temporally associated with COVID-19, the decision to start antiviral or immunomodulatory therapy should be on a case-by-case basis; in the UK, this should be done within a clinical trial. Further research is needed into both the disease course and treatment of paediatric COVID-19.
Published: 2020

47. The Vasculopathy of Juvenile Dermatomyositis: Endothelial Injury, Hypercoagulability, and Increased Arterial Stiffness

Author: Ying Hong, Clarissa Pilkington, Lucy R. Wedderburn, Charalampia Papadopoulou, Despina Eleftheriou, Paul A. Brogan, Petra Krol, and Muthana Al Obaidi
Subjects: Male, medicine.medical_specialty, Adolescent, Immunology, Pulse Wave Analysis, Gastroenterology, Dermatomyositis, Pathogenesis, Vascular Stiffness, Rheumatology, Interquartile range, Cell-Derived Microparticles, Internal medicine, medicine, Immunology and Allergy, Juvenile, Humans, Thrombophilia, Platelet activation, Endothelium, Vascular Diseases, Child, Pulse wave velocity, Juvenile dermatomyositis, business.industry, Case-control study, Thrombin, Endothelial Cells, medicine.disease, Case-Control Studies, Arterial stiffness, Cytokines, Female, Chemokines, business
Abstract: OBJECTIVE Vasculopathy is considered central to the pathogenesis of juvenile dermatomyositis (DM) and is associated with severe extramuscular manifestations. We undertook this study to investigate the hypothesis that the vasculopathy of juvenile DM can be noninvasively tracked by examining biomarkers of endothelial injury, subclinical inflammation, hypercoagulability, and vascular arterial stiffness. METHODS The study population was a UK cohort of children with juvenile DM. Circulating endothelial cells (CECs) and microparticles (MPs) were identified using immunomagnetic bead extraction and flow cytometry, respectively. Plasma thrombin generation was determined using a fluorogenic assay. Cytokine and chemokine levels were measured by electrochemiluminescence. Arterial stiffness was assessed using pulse wave velocity (PWV). Results were expressed as the median and interquartile range (IQR), and statistical significance was assessed using nonparametric analyses. RESULTS Ninety patients with juvenile DM and 79 healthy control subjects were included. The median age of the patients was 10.21 years (IQR 6.68-13.40), and the median disease duration was 1.63 years (IQR 0.28-4.66). CEC counts were higher in all patients with juvenile DM compared to controls (median 96 cells/ml [IQR (40-192] and 12 cells/ml [IQR 8-24], respectively; P < 0.0001). Circulating MP numbers were also significantly higher in patients with active juvenile DM compared to controls (median 204.7 × 103 /ml [IQR 87.9-412.6] and 44.3 × 103 /ml [IQR 15.0-249.1], respectively; P < 0.0001). MPs were predominantly of platelet and endothelial origin. Enhanced plasma thrombin generation was demonstrated in patients with active juvenile DM compared to those with inactive disease (P = 0.0003) and controls (P < 0.0001). Carotid-radial PWV adjusted for age was increased in patients with juvenile DM compared to controls (P = 0.003). CONCLUSION We observed increased endothelial injury and increased levels of proinflammatory cytokines in patients with active juvenile DM. MP profiles reflected distinct disease activity status in juvenile DM and are markers of vascular pathology, platelet activation, and thrombotic propensity. Ongoing long-term vascular injury may result in increased arterial stiffness in patients with juvenile DM.
Published: 2020

48. Pre-existing and de novo humoral immunity to SARS-CoV-2 in humans

Author: Kevin W. Ng, Nikhil Faulkner, Georgina H. Cornish, Annachiara Rosa, Ruth Harvey, Saira Hussain, Rachel Ulferts, Christopher Earl, Antoni Wrobel, Donald Benton, Chloe Roustan, William Bolland, Rachael Thompson, Ana Agua-Doce, Philip Hobson, Judith Heaney, Hannah Rickman, Stavroula Paraskevopoulou, Catherine F. Houlihan, Kirsty Thomson, Emilie Sanchez, David Brealey, Gee Yen Shin, Moira J. Spyer, Dhira Joshi, Nicola O’Reilly, Philip A. Walker, Svend Kjaer, Andrew Riddell, Catherine Moore, Bethany R. Jebson, Meredyth G.Ll. Wilkinson, Lucy R. Marshall, Elizabeth C. Rosser, Anna Radziszewska, Hannah Peckham, Coziana Ciurtin, Lucy R. Wedderburn, Rupert Beale, Charles Swanton, Sonia Gandhi, Brigitta Stockinger, John McCauley, Steve Gamblin, Laura E. McCoy, Peter Cherepanov, Eleni Nastouli, and George Kassiotis
Subjects: chemistry.chemical_classification, education.field_of_study, Zoonotic Infection, viruses, fungi, Population, virus diseases, Biology, medicine.disease_cause, Virology, Nucleoprotein, body regions, chemistry, Immunity, Humoral immunity, medicine, biology.protein, Antibody, skin and connective tissue diseases, education, Glycoprotein, Coronavirus
Abstract: Several related human coronaviruses (HCoVs) are endemic in the human population, causing mild respiratory infections1. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiologic agent of Coronavirus disease 2019 (COVID-19), is a recent zoonotic infection that has quickly reached pandemic proportions2,3. Zoonotic introduction of novel coronaviruses is thought to occur in the absence of pre-existing immunity in the target human population. Using diverse assays for detection of antibodies reactive with the SARS-CoV-2 spike (S) glycoprotein, we demonstrate the presence of pre-existing humoral immunity in uninfected and unexposed humans to the new coronavirus. SARS-CoV-2 S-reactive antibodies were readily detectable by a sensitive flow cytometry-based method in SARS-CoV-2-uninfected individuals and were particularly prevalent in children and adolescents. These were predominantly of the IgG class and targeted the S2 subunit. In contrast, SARS-CoV-2 infection induced higher titres of SARS-CoV-2 S-reactive IgG antibodies, targeting both the S1 and S2 subunits, as well as concomitant IgM and IgA antibodies, lasting throughout the observation period of 6 weeks since symptoms onset. SARS-CoV-2-uninfected donor sera also variably reacted with SARS-CoV-2 S and nucleoprotein (N), but not with the S1 subunit or the receptor binding domain (RBD) of S on standard enzyme immunoassays. Notably, SARS-CoV-2-uninfected donor sera exhibited specific neutralising activity against SARS-CoV-2 and SARS-CoV-2 S pseudotypes, according to levels of SARS-CoV-2 S-binding IgG and with efficiencies comparable to those of COVID-19 patient sera. Distinguishing pre-existing and de novo antibody responses to SARS-CoV-2 will be critical for our understanding of susceptibility to and the natural course of SARS-CoV-2 infection.
Published: 2020

49. O29 Methotrexate response clusters in JIA

Author: Kimme L. Hyrich, Cluster, Bspar-Etn, Bcrd, Nophar Geifman, Stephanie J W Shoop-Worrall, Lucy R. Wedderburn, and Wendy Thomson
Subjects: musculoskeletal diseases, Oncology, medicine.medical_specialty, Rheumatology, business.industry, Internal medicine, medicine, Pharmacology (medical), Methotrexate, business, medicine.drug, Etanercept
Abstract: Background Treatment response in juvenile idiopathic arthritis (JIA) is currently viewed as a binary outcome of response versus non-response. In a heterogenous disease such as JIA, it is likely that different, identifiable clusters of children and young people (CYP) may display varying patterns of the different features of the disease. Identifying these response clusters is an important step toward stratified medicine in JIA. The aim of the study was to explore trajectories of juvenile arthritis disease activity score (JADAS) components following methotrexate (MTX) initiation for JIA. Methods MTX-naïve CYP with JIA were selected if enrolled prior to January 2018 in either the UK BSPAR Etanercept Register or the Biologics for Children with Rheumatic Diseases Study at point of starting MTX. JADAS components (active joint count, physician’s global assessment (0-10cm), parental global evaluation (0-10cm) and standardised ESR (0-10) were calculated based on data collected in the year following MTX initiation. Multivariate group-based trajectory models were used to explore MTX response clusters across the different JADAS components, using censored-normal (global scores, ESR) and zero-inflated Poisson (active joint count) models. Optimal models were selected based on a combination of model fit (BIC), parsimony and clinical plausibility. Results Of 611 CYP selected, the majority were female (69%) and of white ethnicity (85%), with RF-negative JIA the most common disease category (33%). The optimal model identified multiple patterns of disease activity following initiation of MTX, which have greater complexity than simple ‘response’ versus ‘non-response’ clusters. Differences between clusters included initial intensity of disease features and speeds of improvement over time. In addition, the components of the JADAS did not always follow similar patterns over time, even within the same outcome cluster. Conclusion This study has identified that within CYP initiating MTX, different patterns of disease activity are apparent, suggesting that a simple responder/non-responder analysis at a set point may be inadequate. Understanding both clinical factors associated with, and biological mechanisms underpinning, these clusters would aid stratified medicine in JIA. Disclosures S.J.W. Shoop-Worrall None. K.L. Hyrich None. L.R. Wedderburn None. W. Thomson None. N. Geifman None.
Published: 2020

50. O17 Modelling longitudinal patient-reported outcome measures in JDM

Author: Lucy R. Wedderburn, Bianca De Stavola, Edmund Njeru Njagi, Paris J Baptiste, and Claire T Deakin
Subjects: myalgia, medicine.medical_specialty, business.industry, Outcome measures, Muscle weakness, Skin ulcer, medicine.disease, Dermatology, Rheumatology, Patient Self-Report, medicine, Pharmacology (medical), Medical history, Patient-reported outcome, medicine.symptom, business, Juvenile dermatomyositis
Abstract: Background Juvenile dermatomyositis (JDM) is a rare autoimmune disease known to primarily cause rash and muscle weakness. The evolution of the disease is still unclear, in particular disease activity based on patient-reported outcomes. A cohort of 493 patients with 3,625 visits up to 5 years since diagnosis was used to explore disease trajectories based on the patient-reported outcome, patient/parent visual analogue scale (VAS), completed by the appropriate person depending on the child’s age. Age at diagnosis, sex, ethnicity and baseline physician's global assessment (PGA) measurements were considered as predictors of disease activity. In addition to this 8 baseline clinical/medical history variables were also considered as potentially predictive: ulcerations, Gottron’s papules, myalgia, fever, fatigue, dysphagia, respiration and gastrointestinal problems. Methods A mixed effects model was fitted to the data to identify the strongest predictors of disease activity accounting for correlations of patient/parent VAS measurements within patients. Growth mixture models were used to identify subgroups of patients that shared similar trajectories (latent classes) and logistic regression was used to predict the probability of belonging to the subgroup that had more severe disease activity. The identified latent classes of disease activity, based on the patient-reported outcome of patient/parent VAS, were compared with previously identified latent classes derived from PGA as the outcome measure. Results The results from fitting a mixed effects model showed that disease activity had a cubic relationship with time since diagnosis. Being non-white and having a history of myalgia and gastrointestinal problems was shown to predict higher disease activity across the whole follow-up time. The results from fitting growth mixture models led to identifying two classes: the first showed an improvement in condition after the first year, which correlated with results from the mixed effects model, the second, more severe class, was on average higher and showed little improvement across the 5 years. In addition to the predictors identified in the mixed effects model, skin ulceration and older than the mean age (8.3 years) at diagnosis were shown to be associated with the probability of belonging to the more severe class. Conclusion Comparing these results to those previously found in analyses of PGA data collected on the same patients, we found that the patterns of activity were similar although on average higher, indicating that reports of disease activity by patients/parents were worse than those collected from physicians. This could be due to factors influencing patient’s experiences that are not measured by physicians. Discussions with clinicians suggest that this could be due to symptoms that are difficult to measure and that are unaffected by treatment, for example, symptoms causing damage. These are often overlooked in physician’s assessments, despite being an important factor for patients. Disclosures P.J. Baptiste None. L.R. Wedderburn None. C.T. Deakin None. B.L. De Stavola None. E. Njagi None.
Published: 2020

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