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2. Rheumatology

Author

Ludwig, Dalia, primary, Wing, Charlotte, additional, and Manson, Jessica J., additional

Published
2023
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3. Diagnosis and investigation of suspected haemophagocytic lymphohistiocytosis in adults: 2023 Hyperinflammation and HLH Across Speciality Collaboration (HiHASC) consensus guideline

Author

Cox, Miriam F, Mackenzie, Strachan, Low, Ryan, Brown, Michael, Sanchez, Emilie, Carr, Aisling, Carpenter, Ben, Bishton, Mark, Duncombe, Andrew, Akpabio, Akpabio, Kulasekararaj, Austin, Sin, Fang En, Jones, Alexis, Kavirayani, Akhila, Sen, Ethan S, Quick, Vanessa, Dulay, Gurdeep S, Clark, Sam, Bauchmuller, Kris, Tattersall, Rachel S, and Manson, Jessica J

Published
2024
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7. COVID-19-associated hyperinflammation and escalation of patient care: a retrospective longitudinal cohort study

Author

Manson, Jessica J, Crooks, Colin, Naja, Meena, Ledlie, Amanda, Goulden, Bethan, Liddle, Trevor, Khan, Emon, Mehta, Puja, Martin-Gutierrez, Lucia, Waddington, Kirsty E, Robinson, George A, Ribeiro Santos, Liliana, McLoughlin, Eve, Snell, Antonia, Adeney, Christopher, Schim van der Loeff, Ina, Baker, Kenneth F, Duncan, Christopher J A, Hanrath, Aidan T, Lendrem, B Clare, De Soyza, Anthony, Peng, Junjie, J'Bari, Hajar, Greenwood, Mandy, Hawkins, Ellie, Peckham, Hannah, Marks, Michael, Rampling, Tommy, Luintel, Akish, Williams, Bryan, Brown, Michael, Singer, Mervyn, West, Joe, Jury, Elizabeth C, Collin, Matthew, and Tattersall, Rachel S

Published
2020
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18. Diagnosis and investigation of suspected haemophagocytic lymphohistiocytosis in adults: 2023 Hyperinflammation and HLH Across Speciality Collaboration (HiHASC) consensus guideline

Author

Cox, Miriam F, primary, Mackenzie, Strachan, additional, Low, Ryan, additional, Brown, Michael, additional, Sanchez, Emilie, additional, Carr, Aisling, additional, Carpenter, Ben, additional, Bishton, Mark, additional, Duncombe, Andrew, additional, Akpabio, Akpabio, additional, Kulasekararaj, Austin, additional, Sin, Fang En, additional, Jones, Alexis, additional, Kavirayani, Akhila, additional, Sen, Ethan S, additional, Quick, Vanessa, additional, Dulay, Gurdeep S, additional, Clark, Sam, additional, Bauchmuller, Kris, additional, Tattersall, Rachel S, additional, and Manson, Jessica J, additional

Published
2023
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22. P004 Infective complications in patients with secondary haemophagocytic lymphohistiocytosis: a case series from a large central London teaching hospital

Author

Saha, Pratyasha, primary, McCann, Naina, additional, Brown, Michael, additional, Stone, Neil, additional, Sanchez, Emilie, additional, Carpenter, Ben, additional, Laurence, Arian, additional, Hutchinson, Matthew, additional, Jones, Alexis, additional, Gohil, Satyen H, additional, and Manson, Jessica, additional

Published
2023
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25. OA22 Management of haemophagocytic lymphohistiocytosis: service evaluation of a national multi-disciplinary meeting

Author

Shah, Neal S, primary, Hutchinson, Matthew, additional, Clark, Samuel, additional, Sanchez, Emilie, additional, Brown, Michael, additional, Stone, Neil, additional, Carr, Aisling S, additional, Carpenter, Ben, additional, Laurence, Arian, additional, Gohil, Satyen H, additional, Tattersall, Rachel S, additional, Manson, Jessica J, additional, and Jones, Alexis, additional

Published
2023
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26. Clinicogenomic factors of biotherapy immunogenicity in autoimmune disease: A prospective multicohort study of the ABIRISK consortium

Author

Hässler, Signe, Bachelet, Delphine, Duhaze, Julianne, Szely, Natacha, Gleizes, Aude, Hacein-Bey Abina, Salima, Aktas, Orhan, Auer, Michael, Avouac, Jerôme, Birchler, Mary, Bouhnik, Yoram, Brocq, Olivier, Buck-Martin, Dorothea, Cadiot, Guillaume, Carbonnel, Franck, Chowers, Yehuda, Comabella, Manuel, Derfuss, Tobias, De Vries, Niek, Donnellan, Naoimh, Doukani, Abiba, Guger, Michael, Hartung, Hans-Peter, Kubala Havrdova, Eva, Hemmer, Bernhard, Huizinga, Tom, Ingenhoven, Kathleen, Hyldgaard-Jensen, Poul Erik, Jury, Elizabeth C., Khalil, Michael, Kieseier, Bernd, Laurén, Anna, Lindberg, Raija, Loercher, Amy, Maggi, Enrico, Manson, Jessica, Mauri, Claudia, Mohand Oumoussa, Badreddine, Montalban, Xavier, Nachury, Maria, Nytrova, Petra, Richez, Christophe, Ryner, Malin, Sellebjerg, Finn, Sievers, Claudia, Sikkema, Dan, Soubrier, Martin, Tourdot, Sophie, Trang, Caroline, Vultaggio, Alessandra, Warnke, Clemens, Spindeldreher, Sebastian, Dönnes, Pierre, Hickling, Timothy P., Hincelin Mery, Agnès, Allez, Matthieu, Deisenhammer, Florian, Fogdell-Hahn, Anna, Mariette, Xavier, Pallardy, Marc, and Broët, Philippe

Subjects
Drug therapy, Usage, Complications and side effects, Genetic aspects, Health aspects, Autoimmune diseases -- Drug therapy -- Genetic aspects, Biopharmaceuticals -- Usage -- Complications and side effects, Immune response -- Genetic aspects -- Health aspects
Abstract

Author(s): Signe Hässler 1,2,3,*, Delphine Bachelet 1,4, Julianne Duhaze 1,5, Natacha Szely 6, Aude Gleizes 6,7, Salima Hacein-Bey Abina 7,8, Orhan Aktas 9, Michael Auer 10, Jerôme Avouac 11,12, Mary [...], Background Biopharmaceutical products (BPs) are widely used to treat autoimmune diseases, but immunogenicity limits their efficacy for an important proportion of patients. Our knowledge of patient-related factors influencing the occurrence of antidrug antibodies (ADAs) is still limited. Methods and findings The European consortium ABIRISK (Anti-Biopharmaceutical Immunization: prediction and analysis of clinical relevance to minimize the RISK) conducted a clinical and genomic multicohort prospective study of 560 patients with multiple sclerosis (MS, n = 147), rheumatoid arthritis (RA, n = 229), Crohn&apos;s disease (n = 148), or ulcerative colitis (n = 36) treated with 8 different biopharmaceuticals (etanercept, n = 84; infliximab, n = 101; adalimumab, n = 153; interferon [IFN]-beta-1a intramuscularly [IM], n = 38; IFN-beta-1a subcutaneously [SC], n = 68; IFN-beta-1b SC, n = 41; rituximab, n = 31; tocilizumab, n = 44) and followed during the first 12 months of therapy for time to ADA development. From the bioclinical data collected, we explored the relationships between patient-related factors and the occurrence of ADAs. Both baseline and time-dependent factors such as concomitant medications were analyzed using Cox proportional hazard regression models. Mean age and disease duration were 35.1 and 0.85 years, respectively, for MS; 54.2 and 3.17 years for RA; and 36.9 and 3.69 years for inflammatory bowel diseases (IBDs). In a multivariate Cox regression model including each of the clinical and genetic factors mentioned hereafter, among the clinical factors, immunosuppressants (adjusted hazard ratio [aHR] = 0.408 [95% confidence interval (CI) 0.253-0.657], p < 0.001) and antibiotics (aHR = 0.121 [0.0437-0.333], p < 0.0001) were independently negatively associated with time to ADA development, whereas infections during the study (aHR = 2.757 [1.616-4.704], p < 0.001) and tobacco smoking (aHR = 2.150 [1.319-3.503], p < 0.01) were positively associated. 351,824 Single-Nucleotide Polymorphisms (SNPs) and 38 imputed Human Leukocyte Antigen (HLA) alleles were analyzed through a genome-wide association study. We found that the HLA-DQA1*05 allele significantly increased the rate of immunogenicity (aHR = 3.9 [1.923-5.976], p < 0.0001 for the homozygotes). Among the 6 genetic variants selected at a 20% false discovery rate (FDR) threshold, the minor allele of rs10508884, which is situated in an intron of the CXCL12 gene, increased the rate of immunogenicity (aHR = 3.804 [2.139-6.764], p < 1 x 10.sup.-5 for patients homozygous for the minor allele) and was chosen for validation through a CXCL12 protein enzyme-linked immunosorbent assay (ELISA) on patient serum at baseline before therapy start. CXCL12 protein levels were higher for patients homozygous for the minor allele carrying higher ADA risk (mean: 2,693 pg/ml) than for the other genotypes (mean: 2,317 pg/ml; p = 0.014), and patients with CXCL12 levels above the median in serum were more prone to develop ADAs (aHR = 2.329 [1.106-4.90], p = 0.026). A limitation of the study is the lack of replication; therefore, other studies are required to confirm our findings. Conclusion In our study, we found that immunosuppressants and antibiotics were associated with decreased risk of ADA development, whereas tobacco smoking and infections during the study were associated with increased risk. We found that the HLA-DQA1*05 allele was associated with an increased rate of immunogenicity. Moreover, our results suggest a relationship between CXCL12 production and ADA development independent of the disease, which is consistent with its known function in affinity maturation of antibodies and plasma cell survival. Our findings may help physicians in the management of patients receiving biotherapies.

Published
2020
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34. Biomarker and Cytokine Associations with Outcomes in Secondary Haemophagocytic Lymphohistiocytosis: A Scoping Review

Author

Raith, Eamon, Terrett, Alice, Sundararajan, Krishnaswamy, Small, Jillian, Holasek, Anna, Singer, Mervyn, and Manson, Jessica

Subjects
Rheumatology, Critical Care, Immune System Diseases, Medicine and Health Sciences, Medical Specialties, Diseases
Abstract

A broad range of immunomodulatory therapies is used in the management of haemophagocytic lymphohistiocytosis, however supporting evidence for these therapies is scarce. Identifying patients likely to experience more severe disease, or die, is currently extremely difficult, if not impossible. Identification of implicated cytokines in secondary disease can provide further support for identifying high-risk patients, and the development of targeted therapies. This scoping review aims to identify biomarker and cytokine associations with severity of illness and mortality in patients with secondary haemophagocytic lymphohistiocytosis. OVID Medline and EMBASE searches will be conducted, limited to English-language publications, without date limitations, in accordance with the Joanna Briggs Institute methodology for scoping reviews. Data will be extracted using a data extraction tool developed by the reviewers. Relevant sources will be retrieved and their citation details imported into the Joanna Briggs Institute System for the Unified Management, Assessment and Review of Information. Extracted data will be presented in as a narrative summary and associated tables

Published
2022
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35. Understanding the diagnosis and management of multisystem inflammatory syndrome in adults (MIS-A) in the UK: results of a national Delphi process

Author

Hookham, Lauren, Fisher, Corinne, Manson, Jessica J, Morgan, Matt, O'Hara, Geraldine, Riley, Phil, Tattersall, Rachel S, and Goodman, Anna L

Subjects
SARS-CoV-2, COVID-19 rapid report, Aftercare, COVID-19, Humans, General Medicine, Child, Patient Discharge, Systemic Inflammatory Response Syndrome, United Kingdom
Abstract

Infection with SARS-CoV-2 may trigger a delayed hyper-inflammatory illness in children called paediatric multisystem inflammatory syndrome temporally associated with COVID-19 (PIMS-TS). A similar syndrome is increasingly recognised in adults termed multisystem inflammatory syndrome in adults (MIS-A) and may present acutely to medical or surgical specialties with severe symptoms, such as acute abdominal pain or cardiogenic shock. No national guidelines exist in the UK for the management of MIS-A and there is limited evidence to guide treatment plans. We undertook a national Delphi process to elicit opinions from experts in hyperinflammation about the diagnosis and management of MIS-A with the dual aim of improving recognition and producing a management guideline. Colleagues in paediatrics successfully initiated a national consensus management document that facilitated regional multidisciplinary referral and follow-up pathways for children with PIMS-TS, and we propose a similar system be developed for adult patients across the UK. This would facilitate better recognition and treatment of MIS-A across the multiple specialties to which it may present as well as enable follow-up with specialty services post-discharge.

Published
2022

47. Incidence and survival of haemophagocytic lymphohistiocytosis: A population‐based cohort study from England

Author

West, Joe, primary, Card, Tim R., additional, Bishton, Mark J., additional, Lanyon, Peter, additional, Ban, Lu, additional, Bythell, Mary, additional, Elliss‐Brookes, Lucy, additional, Manson, Jessica J., additional, Nanduri, Vasanta, additional, Rankin, Judith, additional, Tattersall, Rachel S., additional, and Crooks, Colin J., additional

Published
2021
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