20 results on '"George Bertsias"'
Search Results
2. Microglia activation in the presence of intact blood–brain barrier and disruption of hippocampal neurogenesis via IL-6 and IL-18 mediate early diffuse neuropsychiatric lupus
- Author
-
Dionysis Nikolopoulos, Theodora Manolakou, Alexia Polissidis, Anastasia Filia, George Bertsias, Yassemi Koutmani, and Dimitrios T Boumpas
- Subjects
Rheumatology ,Immunology ,Immunology and Allergy ,General Biochemistry, Genetics and Molecular Biology - Abstract
IntroductionInflammatory mediators are detected in the cerebrospinal fluid of systemic lupus erythematosus patients with central nervous system involvement (NPSLE), yet the underlying cellular and molecular mechanisms leading to neuropsychiatric disease remain elusive.MethodsWe performed a comprehensive phenotyping of NZB/W-F1 lupus-prone mice including tests for depression, anxiety and cognition. Immunofluorescence, flow cytometry, RNA-sequencing, qPCR, cytokine quantification and blood–brain barrier (BBB) permeability assays were applied in hippocampal tissue obtained in both prenephritic (3-month-old) and nephritic (6-month-old) lupus mice and matched control strains. Healthy adult hippocampal neural stem cells (hiNSCs) were exposedex vivoto exogenous inflammatory cytokines to assess their effects on proliferation and apoptosis.ResultsAt the prenephritic stage, BBB is intact yet mice exhibit hippocampus-related behavioural deficits recapitulating the human diffuse neuropsychiatric disease. This phenotype is accounted by disrupted hippocampal neurogenesis with hiNSCs exhibiting increased proliferation combined with decreased differentiation and increased apoptosis in combination with microglia activation and increased secretion of proinflammatory cytokines and chemokines. Among these cytokines, IL-6 and IL-18 directly induce apoptosis of adult hiNSCs ex vivo. During the nephritic stage, BBB becomes disrupted which facilitates immune components of peripheral blood, particularly B-cells, to penetrate into the hippocampus further augmenting inflammation with locally increased levels of IL-6, IL-12, IL-18 and IL-23. Of note, an interferon gene signature was observed only at nephritic-stage.ConclusionAn intact BBB with microglial activation disrupting the formation of new neurons within the hippocampus represent early events in NPSLE. Disturbances of the BBB and interferon signature are evident later in the course of the disease.
- Published
- 2023
3. Update οn the diagnosis and management of systemic lupus erythematosus
- Author
-
Antonis Fanouriakis, Dimitrios T. Boumpas, Nikolaos Tziolos, and George Bertsias
- Subjects
Systemic disease ,Heart Valve Diseases ,Lupus nephritis ,Uterine Cervical Neoplasms ,Disease ,Severity of Illness Index ,Quality of life ,Pregnancy ,Recurrence ,Azathioprine ,Outcome Assessment, Health Care ,Lupus Erythematosus, Systemic ,Pericarditis ,Immunology and Allergy ,skin and connective tissue diseases ,Macrophage Activation Syndrome ,Lupus Vasculitis, Central Nervous System ,Disease Management ,Prognosis ,Lupus Nephritis ,Survival Rate ,Organ damage ,Myocarditis ,Phenotype ,Cardiovascular Diseases ,Female ,Rituximab ,Immunosuppressive Agents ,Hydroxychloroquine ,medicine.medical_specialty ,Hypertension, Pulmonary ,Calcineurin Inhibitors ,Immunology ,Antibodies, Monoclonal, Humanized ,General Biochemistry, Genetics and Molecular Biology ,Rheumatology ,Internal medicine ,medicine ,Humans ,Intensive care medicine ,Cyclophosphamide ,Glucocorticoids ,Autoantibodies ,Purpura, Thrombocytopenic, Idiopathic ,Lupus erythematosus ,business.industry ,Mycophenolic Acid ,medicine.disease ,Pregnancy Complications ,Methotrexate ,Quality of Life ,Anemia, Hemolytic, Autoimmune ,business ,Rheumatism - Abstract
Clinical heterogeneity, unpredictable course and flares are characteristics of systemic lupus erythematosus (SLE). Although SLE is—by and large—a systemic disease, occasionally it can be organ-dominant, posing diagnostic challenges. To date, diagnosis of SLE remains clinical with a few cases being negative for serologic tests. Diagnostic criteria are not available and classification criteria are often used for diagnosis, yet with significant caveats. Newer sets of criteria (European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019) enable earlier and more accurate classification of SLE. Several disease endotypes have been recognised over the years. There is increased recognition of milder cases at presentation, but almost half of them progress overtime to more severe disease. Approximately 70% of patients follow a relapsing-remitting course, the remaining divided equally between a prolonged remission and a persistently active disease. Treatment goals include long-term patient survival, prevention of flares and organ damage, and optimisation of health-related quality of life. For organ-threatening or life-threatening SLE, treatment usually includes an initial period of high-intensity immunosuppressive therapy to control disease activity, followed by a longer period of less intensive therapy to consolidate response and prevent relapses. Management of disease-related and treatment-related comorbidities, especially infections and atherosclerosis, is of paramount importance. New disease-modifying conventional and biologic agents—used alone, in combination or sequentially—have improved rates of achieving both short-term and long-term treatment goals, including minimisation of glucocorticoid use.
- Published
- 2020
4. In an early SLE cohort the ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria classify non-overlapping groups of patients: use of all three criteria ensures optimal capture for clinical studies while their modification earlier classification and treatment
- Author
-
Irini Genitsaridi, Dimitrios T. Boumpas, Alessandra Bortoluzzi, George Bertsias, Dionysis Nikolopoulos, Prodromos Sidiropoulos, Christina Adamichou, Irini Gergianaki, Emmanouil Papastefanakis, Eleni Kalogiannaki, and Antonis Fanouriakis
- Subjects
Adult ,Male ,musculoskeletal diseases ,medicine.medical_specialty ,Immunology ,Disease ,Sensitivity and Specificity ,Severity of Illness Index ,General Biochemistry, Genetics and Molecular Biology ,NO ,autoimmune diseases, outcomes research, systemic lupus erythematosus ,outcomes research ,systemic lupus erythematosus ,Rheumatology ,Internal medicine ,Humans ,Lupus Erythematosus, Systemic ,Immunology and Allergy ,Medicine ,autoimmune diseases ,skin and connective tissue diseases ,Disease burden ,Retrospective Studies ,High prevalence ,Systemic lupus erythematosus ,business.industry ,Middle Aged ,medicine.disease ,Cohort ,Female ,Symptom Assessment ,Outcomes research ,business ,Algorithms ,Rheumatism - Abstract
ObjectivesClassification criteria are biased towards classifying long-standing disease. We compared the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR)-2019, Systemic Lupus International Collaborating Clinics (SLICC)-2012 and ACR-1997 criteria in an early (median 48 months) systemic lupus erythematosus (SLE) cohort.MethodsPatients diagnosed with SLE (n=690) or control diseases (n=401). Sensitivity, specificity of the criteria and time-to-classification were calculated. Modified classification algorithms were derived from a random 80% and validated in the remaining 20% of the dataset running multiple iterations.ResultsAt last assessment, sensitivities of ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria were 85.7%, 91.3% and 88.6%, with specificities 93.0%, 93.8% and 97.3%, respectively. Both SLICC and EULAR/ACR enabled earlier classification. Only 76.7% of patients with SLE met all three criteria suggesting non-overlapping groups. Notably, unclassified patients had high prevalence of British Isles Lupus Assessment Group moderate/severe manifestations (43.3%–60%) and SLICC/ACR organ damage (30%–50%). At diagnosis, criteria missed 25.6%–30.5% of patients. Modification of EULAR/ACR and SLICC algorithms to include hypocomplementaemia and/or positive anti-phospholipid antibodies as alternative entry criterion, and/or allow classification with fewer clinical criteria from multiple organs, increased their sensitivity at diagnosis (median 82.0% and 86.2%) and overall (93.7% and 97.1%) with modest decreases in specificity. Importantly, patients who were still missed by the modified criteria had lower incidence of major organ involvement, use of immunosuppressive/biological therapies and organ damage.ConclusionsThe SLICC and EULAR/ACR are more sensitive than the ACR and the EULAR/ACR criteria have superior specificity in early SLE, although patients with significant disease can be missed. Combination and/or modification of the classification algorithms may enhance their sensitivity, allowing earlier classification and treatment of more patients with high disease burden.
- Published
- 2019
5. REDD1/autophagy pathway promotes thromboinflammation and fibrosis in human systemic lupus erythematosus (SLE) through NETs decorated with tissue factor (TF) and interleukin-17A (IL-17A)
- Author
-
Eleni Frangou, Stella Arelaki, Dimitrios T. Boumpas, George Bertsias, Hariklia Gakiopoulou, Alexandros Mitsios, Panayotis Verginis, Konstantinos Ritis, Athanasios Arampatzioglou, Iliana Angelidou, Konstantinos Kambas, and Akrivi Chrysanthopoulou
- Subjects
0301 basic medicine ,autophagy ,Immunology ,Cell Culture Techniques ,Extracellular Traps ,Systemic Lupus Erythematosus ,General Biochemistry, Genetics and Molecular Biology ,Thromboplastin ,Pathogenesis ,03 medical and health sciences ,Tissue factor ,0302 clinical medicine ,neutrophils ,Rheumatology ,Fibrosis ,medicine ,Humans ,Lupus Erythematosus, Systemic ,Immunology and Allergy ,skin and connective tissue diseases ,Inflammation ,030203 arthritis & rheumatology ,Systemic lupus erythematosus ,business.industry ,Interleukin-17 ,fibrosis ,Autophagy ,Thrombosis ,Hydroxychloroquine ,lupus ,Neutrophil extracellular traps ,Fibroblasts ,medicine.disease ,3. Good health ,030104 developmental biology ,thromboinflammation ,Interleukin 17 ,business ,Signal Transduction ,Transcription Factors ,medicine.drug - Abstract
ObjectivesThe release of neutrophil extracellular traps (NETs) represents a novel neutrophil effector function in systemic lupus erythematosus (SLE) pathogenesis. However, the molecular mechanism underlying NET release and how NETs mediate end-organ injury in SLE remain elusive.MethodsNET formation and NET-related proteins were assessed in the peripheral blood and biopsies from discoid lupus and proliferative nephritis, using immunofluorescence, immunoblotting, quantitative PCR and ELISA. Autophagy was assessed by immunofluorescence and immunoblotting. The functional effects of NETs in vitro were assessed in a primary fibroblast culture.ResultsNeutrophils from patients with active SLE exhibited increased basal autophagy levels leading to enhanced NET release, which was inhibited in vitro by hydroxychloroquine. NETosis in SLE neutrophils correlated with increased expression of the stress-response protein REDD1. Endothelin-1 (ET-1) and hypoxia-inducible factor-1α (HIF-1α) were key mediators of REDD1-driven NETs as demonstrated by their inhibition with bosentan and L-ascorbic acid, respectively. SLE NETs were decorated with tissue factor (TF) and interleukin-17A (IL-17A), which promoted thrombin generation and the fibrotic potential of cultured skin fibroblasts. Notably, TF-bearing and IL-17A-bearing NETs were abundant in discoid skin lesions and in the glomerular and tubulointerstitial compartment of proliferative nephritis biopsy specimens.ConclusionsOur data suggest the involvement of REDD1/autophagy/NET axis in end-organ injury and fibrosis in SLE, a likely candidate for repositioning of existing drugs for SLE therapy. Autophagy-mediated release of TF-bearing and IL-17A-bearing NETs provides a link between thromboinflammation and fibrosis in SLE and may account for the salutary effects of hydroxychloroquine.
- Published
- 2018
6. European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) SLE classification criteria item performance
- Author
-
Carlos Vasconcelos, Zahi Touma, Elena Massarotti, Chiara Tani, Ivan Padjen, Gabriela Schmajuk, Ricard Cervera, Guillermo Ruiz-Irastorza, Matthias Schneider, Florence Assan, Edward M Vital, Bernadett Halda-Kiss, Pier Luigi Meroni, Marvin J. Fritzler, Georg Stummvoll, Murray B. Urowitz, Diane L. Kamen, Dinesh Khanna, Maria G Tektonidou, Falk Hiepe, Raphaèle Seror, Søren Jacobsen, Michelle Jung, Marta Mosca, Sule Yavuz, László Czirják, Winfried Graninger, Sara K. Tedeschi, Bimba F. Hoyer, David I. Daikh, Bevra H. Hahn, Karen H. Costenbader, Rosalind Ramsey-Goldman, David Wofsy, Sindhu R. Johnson, Ann E. Clarke, Joseph M. McCune, Nicolai Leuchten, Kirsten Lerstrøm, Yoshiya Tanaka, Betty Diamond, David Jayne, Peter M. Izmirly, Josef S Smolen, George Bertsias, Ralph Brinks, Dimitrios T. Boumpas, Ray Naden, Juanita Romero-Diaz, Mary K. Crow, Gábor Kumánovics, Iñigo Rúa-Figueroa, Daniel J. Wallace, Thomas Dörner, José M. Pego-Reigosa, Jorge Sanchez-Guerrero, Martin Aringer, Xavier Mariette, Branimir Anić, Sarfaraz Hasni, Andrea Doria, Dafna D. Gladman, Nathalie Costedoat-Chalumeau, Tak Mao Chan, Aringer, Martin [0000-0003-4471-8375], Dörner, Thomas [0000-0002-6478-7725], Boumpas, Dimitrios T [0000-0002-9812-4671], Costedoat-Chalumeau, Nathalie [0000-0002-1555-9021], Diamond, Betty [0000-0002-3250-3804], Gladman, Dafna D [0000-0002-9074-0592], Khanna, Dinesh [0000-0003-1412-4453], Ruiz-Irastorza, Guillermo [0000-0001-7788-1043], Urowitz, Murray [0000-0001-7506-9166], Tedeschi, Sara K [0000-0001-9475-1363], Touma, Zahi [0000-0001-5177-2076], Assan, Florence [0000-0001-6988-6178], Crow, Mary K [0000-0002-7881-2020], Doria, Andrea [0000-0003-0548-4983], Rúa-Figueroa, Íñigo [0000-0002-7894-1690], Tanaka, Yoshiya [0000-0002-0807-7139], Tektonidou, Maria G [0000-0003-2238-0975], Vital, Edward M [0000-0003-1637-4755], Wallace, Daniel J [0000-0002-2502-1372], Yavuz, Sule [0000-0001-5053-6426], Meroni, Pier Luigi [0000-0002-3394-1451], Fritzler, Marvin J [0000-0003-1652-6608], Johnson, Sindhu R [0000-0003-0591-2976], and Apollo - University of Cambridge Repository
- Subjects
musculoskeletal diseases ,medicine.medical_specialty ,Anti-nuclear antibody ,autoantibodies ,Immunology ,Population ,Acr criteria ,Sensitivity and Specificity ,General Biochemistry, Genetics and Molecular Biology ,Cohort Studies ,Rheumatology ,immune system diseases ,Internal medicine ,Rheumatic Diseases ,medicine ,Immunology and Allergy ,antibodies ,Humans ,Lupus Erythematosus, Systemic ,education ,skin and connective tissue diseases ,education.field_of_study ,Lupus erythematosus ,business.industry ,Autoantibody ,systemic ,medicine.disease ,United States ,antiphospholipid ,lupus erythematosus ,synovitis ,Antibodies, Antinuclear ,Delirium ,medicine.symptom ,business ,Rheumatism - Abstract
Background/objectives The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria for systemic lupus erythematosus system showed high specificity, while attaining also high sensitivity. We hereby analysed the performance of the individual criteria items and their contribution to the overall performance of the criteria. Methods We combined the EULAR/ACR derivation and validation cohorts for a total of 1197 systemic lupus erythematosus (SLE) and n=1074 non-SLE patients with a variety of conditions mimicking SLE, such as other autoimmune diseases, and calculated the sensitivity and specificity for antinuclear antibodies (ANA) and the 23 specific criteria items. We also tested performance omitting the EULAR/ACR criteria attribution rule, which defines that items are only counted if not more likely explained by a cause other than SLE. Results Positive ANA, the new entry criterion, was 99.5% sensitive, but only 19.4% specific, against a non-SLE population that included other inflammatory rheumatic, infectious, malignant and metabolic diseases. The specific criteria items were highly variable in sensitivity (from 0.42% for delirium and 1.84% for psychosis to 75.6% for antibodies to double-stranded DNA), but their specificity was uniformly high, with low C3 or C4 (83.0%) and leucopenia Conclusions Changing the position of the highly sensitive, non-specific ANA to an entry criterion and the attribution rule resulted in a specificity of >80% for all items, explaining the higher overall specificity of the criteria set.
- Published
- 2021
- Full Text
- View/download PDF
7. Performance of the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus in early disease, across sexes and ethnicities
- Author
-
Diane L. Kamen, Pier Luigi Meroni, Sarfaraz Hasni, Martin Aringer, Edward M Vital, Xavier Mariette, Maria G Tektonidou, Jorge Sanchez-Guerrero, Michelle Jung, Falk Hiepe, Gábor Kumánovics, Carlos Vasconcelos, George Bertsias, David Jayne, Branimir Anić, Juanita Romero-Diaz, Marta Mosca, Nathalie Costedoat-Chalumeau, Ivan Padjen, Ricard Cervera, László Czirják, Dafna D. Gladman, Bimba F. Hoyer, Søren Jacobsen, Sindhu R. Johnson, Zahi Touma, Kirsten Lerstrøm, Tak Mao Chan, Florence Assan, David I. Daikh, Karen H. Costenbader, Rosalind Ramsey-Goldman, Sara K. Tedeschi, Guillermo Ruiz-Irastorza, Elena Massarotti, Chiara Tani, Josef S Smolen, Andrea Doria, Betty Diamond, Mary K. Crow, Bernadett Halda-Kiss, Ralph Brinks, Murray B. Urowitz, Bevra H. Hahn, Iñigo Rúa-Figueroa, Winfried Graninger, Sule Yavuz, Daniel J. Wallace, José M. Pego-Reigosa, Nicolai Leuchten, Peter M. Izmirly, Ray Naden, Thomas Dörner, Dinesh Khanna, Raphaèle Seror, David Wofsy, Ann E. Clarke, Joseph M. McCune, Matthias Schneider, Georg Stummvoll, Gabriela Schmajuk, Yoshiya Tanaka, Marvin J. Fritzler, Dimitrios T. Boumpas, Johnson, Sindhu R [0000-0003-0591-2976], Boumpas, Dimitrios T [0000-0002-9812-4671], Costedoat-Chalumeau, Nathalie [0000-0002-1555-9021], Gladman, Dafna D [0000-0002-9074-0592], Khanna, Dinesh [0000-0003-1412-4453], Ruiz-Irastorza, Guillermo [0000-0001-7788-1043], Urowitz, Murray [0000-0001-7506-9166], Assan, Florence [0000-0001-6988-6178], Doria, Andrea [0000-0003-0548-4983], Rúa-Figueroa, Íñigo [0000-0002-7894-1690], Tanaka, Yoshiya [0000-0002-0807-7139], Tektonidou, Maria G [0000-0003-2238-0975], Yavuz, Sule [0000-0001-5053-6426], Meroni, Pier Luigi [0000-0002-3394-1451], Dörner, Thomas [0000-0002-6478-7725], Aringer, Martin [0000-0003-4471-8375], and Apollo - University of Cambridge Repository
- Subjects
musculoskeletal diseases ,Male ,medicine.medical_specialty ,Immunology ,Lupus nephritis ,Ethnic group ,Sensitivity and Specificity ,Severity of Illness Index ,General Biochemistry, Genetics and Molecular Biology ,outcomes research ,Rheumatology ,systemic lupus erythematosus ,immune system diseases ,Internal medicine ,Epidemiology ,medicine ,Immunology and Allergy ,Humans ,Lupus Erythematosus, Systemic ,skin and connective tissue diseases ,epidemiology ,lupus nephritis ,business.industry ,Patient Selection ,Early disease ,medicine.disease ,Cohort ,Female ,Outcomes research ,business ,Rheumatism - Abstract
Funder: American College of Rheumatology Research and Education Foundation; FundRef: http://dx.doi.org/10.13039/100000960, Funder: National Institute of Arthritis and Musculoskeletal and Skin Diseases; FundRef: http://dx.doi.org/10.13039/100000069, Funder: European League Against Rheumatism; FundRef: http://dx.doi.org/10.13039/501100008741, OBJECTIVES: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 Classification Criteria for systemic lupus erythematosus (SLE) have been validated with high sensitivity and specificity. We evaluated the performance of the new criteria with regard to disease duration, sex and race/ethnicity, and compared its performance against the Systemic Lupus International Collaborating Clinics (SLICC) 2012 and ACR 1982/1997 criteria. METHODS: Twenty-one SLE centres from 16 countries submitted SLE cases and mimicking controls to form the validation cohort. The sensitivity and specificity of the EULAR/ACR 2019, SLICC 2012 and ACR 1982/1997 criteria were evaluated. RESULTS: The cohort consisted of female (n=1098), male (n=172), Asian (n=118), black (n=68), Hispanic (n=124) and white (n=941) patients; with an SLE duration of 1 to
- Published
- 2020
8. Epidemiology and burden of systemic lupus erythematosus in a Southern European population: data from the community-based lupus registry of Crete, Greece
- Author
-
Alexandra Pompieri, Antonios Bertsias, Dimitrios T. Boumpas, Antonis Fanouriakis, Prodromos Sidiropoulos, Michalis Tzanakakis, Christina Adamichou, Giorgis Spirou, Ioannis Tzanakis, Leda Chatzi, George Bertsias, Irini Gergianaki, Argyro Repa, Eleni Kabouraki, Complexe Genetica, RS: NUTRIM - R4 - Gene-environment interaction, and RS: NUTRIM - R3 - Respiratory & Age-related Health
- Subjects
Male ,Rural Population ,Pediatrics ,Urban Population ,Lupus nephritis ,0302 clinical medicine ,Cost of Illness ,Epidemiology ,Lupus Erythematosus, Systemic ,Immunology and Allergy ,Registries ,030212 general & internal medicine ,DISEASE-ACTIVITY INDEX ,Community based ,education.field_of_study ,Systemic lupus erythematosus ,Greece ,Incidence ,Incidence (epidemiology) ,Lupus Vasculitis, Central Nervous System ,STAGE RENAL-DISEASE ,Middle Aged ,Lupus Nephritis ,COLLEGE-OF-RHEUMATOLOGY ,PREVALENCE ,Female ,Neuropsychiatric disease ,Adult ,medicine.medical_specialty ,Adolescent ,Immunology ,Population ,CLINICS CLASSIFICATION CRITERIA ,White People ,General Biochemistry, Genetics and Molecular Biology ,Young Adult ,03 medical and health sciences ,Age Distribution ,Rheumatology ,medicine ,Humans ,DAMAGE INDEX ,NEPHRITIS ,education ,030203 arthritis & rheumatology ,business.industry ,NORTHWEST GREECE ,UPDATED VERSION ,European population ,medicine.disease ,business ,BILAG 2004 - Abstract
ObjectivesSeveral population-based studies on systemic lupus erythematosus (SLE) have been reported, yet community-based, individual-case validated, comprehensive reports are missing. We studied the SLE epidemiology and burden on the island of Crete during 1999–2013.MethodsMultisource case-finding included patients ≥15 years old. Cases were ascertained by the ACR 1997, SLICC 2012 criteria and rheumatologist diagnosis, and validated through synthesis of medical charts, administrative and patient-generated data.ResultsOverall age-adjusted/sex-adjusted incidence was 7.4 (95% CI 6.8 to 7.9) per 100 000 persons/year, with stabilising trends in women but increasing in men, and average (±SD) age of diagnosis at 43 (±15) years. Adjusted and crude prevalence (December 2013) was 123.4 (113.9 to 132.9) and 143 (133 to 154)/105 (165/105 in urban vs 123/105 in rural regions, pConclusionsBy the use of a comprehensive methodology, we describe the full spectrum of SLE from the community to tertiary care, with almost half of the cases having mild disease, yet with significant damage accrual. SLE is not rare, affects predominantly middle-aged women and is increasingly recognised in men. Neuropsychiatric disease is an emerging frontier in lupus prevention and care.
- Published
- 2017
9. Population-based studies in systemic lupus erythematosus: immune thrombocytopenic purpura or ‘blood-dominant’ lupus?
- Author
-
Dimitrios T. Boumpas, Antonis Fanouriakis, and George Bertsias
- Subjects
Purpura, Thrombocytopenic, Idiopathic ,education.field_of_study ,Lupus erythematosus ,Systemic lupus erythematosus ,business.industry ,Immunology ,Population ,Autoantibody ,Disease ,medicine.disease ,Thrombocytopenic purpura ,General Biochemistry, Genetics and Molecular Biology ,Cohort Studies ,Immune system ,medicine.anatomical_structure ,Rheumatology ,medicine ,Humans ,Lupus Erythematosus, Systemic ,Immunology and Allergy ,Bone marrow ,education ,business - Abstract
Thanks to their large sample size, thus reducing the risk of selection and participation bias, population-based studies can provide high-quality data on the prevalence and incidence, natural history and treatment, correlates and associations of a disease, and healthcare utilisation.1 Several nationwide research databases exist in the world, one of the oldest in Sweden dating back to 1955. The Taiwan National Health Insurance Research Database (NHIRD) is one of the largest nationwide population databases, covering approximately 23 million residents in Taiwan and data of more than 99% of the population. Using this unique database, investigators have asked important questions regarding the heredity and coaggregation of autoimmune diseases, such as systemic lupus erythematosus (SLE), Sjogren’s syndrome and myasthenia gravis.2–4 Immune thrombocytopenic purpura (ITP), formerly known as idiopathic thrombocytopenic purpura, is an immune-mediated acquired disease of adults and children characterised by a transient or persistent decrease of platelet counts and, depending on the degree of thrombocytopenia, increased risk of bleeding.5 In ΙΤP, an abnormal T cell response, supported by splenic T follicular helper cells, stimulates the proliferation and differentiation of autoreactive B cells producing antiplatelet autoantibodies that facilitate platelet phagocytosis by macrophages, predominantly in the spleen. Macrophages also contribute to the perpetuation of the autoimmune response in ITP, functioning as the principal antigen-presenting cells. Inappropriate bone marrow production due to an immune response against megakaryocytes may also exacerbate thrombocytopenia, while the level of …
- Published
- 2020
10. POS0370 TYPE I INTERFERON PATHWAY ASSAYS IN PATIENTS WITH RHEUMATIC AND MUSCULOSKELETAL DISEASES - SYSTEMATIC LITERATURE REVIEW (SLR) AND DEVELOPMENT OF CONSENSUS TERMINOLOGY FROM A EULAR TASKFORCE
- Author
-
P.G. Conaghan, M. Visser, George Bertsias, R. Biesen, Maija-Leena Eloranta, W. A. Dik, G. Cavalli, J Rodríguez Carrio, Marjan A. Versnel, E.M. Vital, Agata Burska, Dimitrios T. Boumpas, Lars Rönnblom, J. Rehwinkel, Marie Wahren-Herlenius, M. L. Frémond, and M. K. Crow
- Subjects
medicine.medical_specialty ,business.industry ,Immunology ,General Biochemistry, Genetics and Molecular Biology ,Terminology ,Systematic review ,Rheumatology ,Interferon ,Immunology and Allergy ,Medicine ,In patient ,business ,Intensive care medicine ,medicine.drug - Abstract
Background:The interferon (IFN) pathway is a complex system with multiple proteins and diverse downstream effects on gene and protein expression. IFNs have been implicated in multiple RMDs. Despite significant potential, IFN assays have not progressed into clinical practice.Objectives:To perform a SLR on IFN assays in RMDs and propose a consensus terminology.Methods:OvidMedline, Embase and Web of Science were searched for reports of IFN and RMDs up to October 2019. Information about the properties of assays measuring type I IFN and measures of truth were extracted and summarised. Terminology was agreed through an interactive consensus process with reference to the existing evidence.Results:10037 abstracts were identified. 275 fulfilled eligibility criteria, and were used for data extraction. Some used more than one technique to measure IFN-I pathway activation. Hence, 275 papers generated data on 393 methods. There was great heterogeneity in the methods used and presentation of results. IFN-I pathway activation was measured using: qPCR (n=121), immunoassays (n=101), microarray (n=69), reporter cell assay (n=38), DNA methylation (n=14), flow cytometry (n=14), cytopathic effect assay (n=11), RNA sequencing (n=9), Plaque reduction assay (n=8), Nanostring (n=5), bisulphite sequencing (n=3). All papers fulfilled Face Validity. Due to lack of gold standard for IFN-I pathway activation, evidence of criterion validity was variable. Concurrent validity was presented for n=150 assays. The terminology used to describe aspects of type I IFN pathway activation was not consistent, so a consensus terminology for IFN research (Table 1) was proposed by the taskforce.Table 1.Consensus terminologyTermAbbreviationDefinitionInterferonIFNProteins with anti-viral activity; IFNs are mediators of an anti-viral response. They belong to the Type I, Type II and Type III IFN families.Type I interferonIFN-IThe IFNs alpha, beta, omega, kappa, epsilon, secreted by any nucleated cell, and binding to the IFNAR, which is expressed on any nucleated cell.Type II interferonIFN-IIIFN gamma, mostly secreted by T cells, binding to the IFNGR, which is expressed on most leucocytes.Type III interferonIFN-IIIIFN lambda, which are structurally more similar to IL-10 but share downstream signalling and gene expression with IFN-I.Interferon-stimulated genesISGsGenes whose expression is known to be upregulated by any kind of IFN. Individual ISGs may not exclusively represent Type I IFN pathway activation.Type I Interferon pathway activationAny evidence for function of the components of the Type I IFN pathway. This includes: secretion of a Type I IFN protein, binding to the IFNAR, initiation of JAK/STAT signalling pathways, expression of IFN-stimulated genes, expression of IFN-stimulated proteins.Type I interferon pathway assayAn assay measuring one or more components of the Type I IFN pathway at a molecular or functional level.Interferon stimulated gene expression signatureA qualitative description of coordinated expression of a set of ISGs that is indicative of Type I IFN pathway activation.Interferon stimulated gene expression scoreA quantitative variable derived from expression of a defined set of ISGs that is indicative of Type I IFN pathway activation.Interferon stimulated protein scoreA variable derived from expression of a defined set of soluble biomarkers known to be upregulated by IFN, although not specific for Type I IFN.InterferonopathyMonogenic diseases in which there is constitutive Type I IFN pathway activation with a causal role in pathology. The clinical picture may resemble rheumatic musculoskeletal diseases. However, most diseases with IFN pathway activation are not Interferonopathies.Conclusion:Diverse methods have been reported as IFN assays and these differ in what elements of type IFN-I pathway activation they measure. The taskforce consensus terminology on type I IFN reporting should be considered for research and clinical applications.Disclosure of Interests:Agata Burska: None declared, Javier Rodriguez Carrio: None declared, Philip G Conaghan: None declared, Willem A Dik: None declared, Robert Biesen: None declared, Maija-leena Eloranta: None declared, Giulio Cavalli: None declared, Marianne Visser: None declared, Dimitrios Boumpas: None declared, George Bertsias: None declared, Marie Wahren-Herlenius: None declared, Jan Rehwinkel: None declared, Marie-Louise Frémond: None declared, Mary K. Crow Consultant of: AstraZeneca, Bristol Meyers Squibb, Lilly, Shannon Pharmaceuticals, Grant/research support from: Gilead, Lars Ronnblom Consultant of: AstraZeneca, Edward Vital Speakers bureau: GSK, Consultant of: AURINIA, SANDOZ, GSK, AstraZeneca, Roche, Modus, Grant/research support from: AstraZeneca, Marjan Versnel: None declared
- Published
- 2021
11. 2008–2018: a decade of recommendations for systemic lupus erythematosus
- Author
-
George Bertsias, Antonis Fanouriakis, and Dimitrios T. Boumpas
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Operating procedures ,education ,Immunology ,Lupus nephritis ,Disease ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,systemic lupus erythematosus ,Rheumatology ,Health care ,Humans ,Lupus Erythematosus, Systemic ,Immunology and Allergy ,Medicine ,skin and connective tissue diseases ,lupus nephritis ,030203 arthritis & rheumatology ,Systemic lupus erythematosus ,treatment ,business.industry ,Hispanic or Latino ,Recommendation ,medicine.disease ,United States ,Clinical Practice ,Clinical trial ,Latin America ,030104 developmental biology ,Family medicine ,business ,Rheumatism - Abstract
Systemic lupus erythematosus (SLE), a complex and heterogeneous autoimmune disease, represents a significant challenge for both diagnosis and treatment. Patients with SLE in Latin America face special problems that should be considered when therapeutic guidelines are developed. The objective of the study is to develop clinical practice guidelines for Latin American patients with lupus. Two independent teams (rheumatologists with experience in lupus management and methodologists) had an initial meeting in Panama City, Panama, in April 2016. They selected a list of questions for the clinical problems most commonly seen in Latin American patients with SLE. These were addressed with the best available evidence and summarised in a standardised format following the Grading of Recommendations Assessment, Development and Evaluation approach. All preliminary findings were discussed in a second face-to-face meeting in Washington, DC, in November 2016. As a result, nine organ/system sections are presented with the main findings; an ‘overarching’ treatment approach was added. Special emphasis was made on regional implementation issues. Best pharmacologic options were examined for musculoskeletal, mucocutaneous, kidney, cardiac, pulmonary, neuropsychiatric, haematological manifestations and the antiphospholipid syndrome. The roles of main therapeutic options (ie, glucocorticoids, antimalarials, immunosuppressant agents, therapeutic plasma exchange, belimumab, rituximab, abatacept, low-dose aspirin and anticoagulants) were summarised in each section. In all cases, benefits and harms, certainty of the evidence, values and preferences, feasibility, acceptability and equity issues were considered to produce a recommendation with special focus on ethnic and socioeconomic aspects. Guidelines for Latin American patients with lupus have been developed and could be used in similar settings.
- Published
- 2018
12. Response to: ‘Bone health, an often forgotten comorbidity in systemic lupus erythematosus: a comment on the new recommendations’ by Orsolini et al
- Author
-
George Bertsias, Antonis Fanouriakis, and Dimitrios T. Boumpas
- Subjects
030203 arthritis & rheumatology ,0301 basic medicine ,medicine.medical_specialty ,Systemic lupus erythematosus ,business.industry ,Immunology ,Osteoporosis ,Disease ,medicine.disease ,Comorbidity ,Bone health ,General Biochemistry, Genetics and Molecular Biology ,Unmet needs ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Rheumatology ,immune system diseases ,medicine ,Immunology and Allergy ,In patient ,skin and connective tissue diseases ,Intensive care medicine ,business ,Rheumatism - Abstract
We thank Drs Orsolini et al for their interest in the updated European League against Rheumatism (EULAR) recommendations for the treatment of systemic lupus erythematosus (SLE),1 and we are grateful for bringing up a crucial aspect of the disease, namely osteoporosis and bone health in patients with this disease. Undoubtedly, prevention and treatment of osteoporosis represent a major challenge and a current unmet need in the holistic management of patients with lupus. The choice …
- Published
- 2019
13. Response to: ‘Concerns about the operational definition of remission in 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus’ by Rua-Figueroa and Erausquin
- Author
-
Antonis Fanouriakis, Dimitrios T. Boumpas, and George Bertsias
- Subjects
030203 arthritis & rheumatology ,0301 basic medicine ,medicine.medical_specialty ,Operational definition ,business.industry ,Immunology ,Hydroxychloroquine ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Disease activity ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Rheumatology ,Research Design ,Humans ,Lupus Erythematosus, Systemic ,Immunology and Allergy ,Medicine ,In patient ,skin and connective tissue diseases ,business ,Intensive care medicine ,Rheumatism ,medicine.drug - Abstract
We thank Drs Rua-Figueroa and Erausquin for their interest in our manuscript and their insightful comment regarding our definition of remission in Figure 1 of the 2019 update of the European League Against Rheumatism recommendations for the management of systemic lupus erythematosus (SLE).1 2 The authors claim that the definition of remission in Figure 1 (SLEDAI 0, only on hydroxychloroquine) is too stringent, as it may guide physicians towards intensification of therapy in patients with sole serological activity. Instead, …
- Published
- 2019
14. Hydroxychloroquine dosing in systemic lupus erythematosus: response to ‘Comment on the 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus by Fanouriakiset al’by Costedoat-Chalumeauet al
- Author
-
Antonis Fanouriakis, Dimitrios T. Boumpas, and George Bertsias
- Subjects
medicine.medical_specialty ,Systemic lupus erythematosus ,business.industry ,Immunology ,Hydroxychloroquine ,medicine.disease ,Dermatology ,General Biochemistry, Genetics and Molecular Biology ,Patient population ,Rheumatology ,Older patients ,Rheumatoid arthritis ,medicine ,Immunology and Allergy ,Dosing ,business ,medicine.drug - Abstract
We thank Drs Costedoat-Chalumeau, Isenberg and Petri for their interest and insightful comments regarding hydroxychloroquine (HCQ) dosing in systemic lupus erythematosus (SLE).1 The authors outline three major arguments against recommending a lower daily dose for HCQ: (1) the lower dose of 5 mg/kg real weight/day has not proven equal efficacy with the previous 6.5 mg/kg/day, (2) the patient population of the studies that suggest higher rates of HCQ-retinopathy (older patients, mostly with rheumatoid arthritis) does not correspond to the average patient with lupus and (3) established low adherence rates to HCQ reported in some studies, if combined with a lower prescribed dose, may potentially lead to HCQ …
- Published
- 2019
15. Chloroquine as alternative antimalarial in systemic lupus erythematosus. Response to ‘2019 update of the EULAR recommendations for the management of SLE: don’t forget chloroquine’ by Figueroa-Parra et al
- Author
-
George Bertsias, Antonis Fanouriakis, and Dimitrios T. Boumpas
- Subjects
medicine.medical_specialty ,business.industry ,Immunology ,Chloroquine ,Dermatology ,General Biochemistry, Genetics and Molecular Biology ,Disease activity ,Antimalarials ,Rheumatology ,Humans ,Lupus Erythematosus, Systemic ,Immunology and Allergy ,Medicine ,business ,Value (mathematics) ,medicine.drug - Abstract
We thank Drs Figueroa-Parra et al for their interest in our paper1 and their comment regarding the value of chloroquine (CQ) as an alternative antimalarial in systemic lupus erythematosus (SLE).2 As the authors point out, there are data, mostly for older studies, to …
- Published
- 2019
16. EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: report of a task force of the EULAR standing committee for clinical affairs
- Author
-
Maria G Tektonidou, Edward L.E.M. Bollen, R. van Vollenhoven, Caroline Gordon, Ian N. Bruce, N Scolding, John G. Hanly, David A. Isenberg, Stefano Bombardieri, M. M. Ward, George Bertsias, Marinos C. Dalakas, C. G. M. Kallenberg, Dimitrios T. Boumpas, John P. A. Ioannidis, Matthias Schneider, Twj Huizinga, M.A. van Buchem, Ricard Cervera, Angela Tincani, A Stara, Martin Aringer, Ioannis Tassiulas, Andrea Doria, Josef S Smolen, and J.C. Piette
- Subjects
COGNITIVE DYSFUNCTION ,medicine.medical_specialty ,Immunology ,Evidence-Based Medicine/methods ,EMISSION COMPUTED-TOMOGRAPHY ,Diagnostic Techniques, Neurological ,RECURRENT THROMBOSIS ,Spinal Cord Diseases ,General Biochemistry, Genetics and Molecular Biology ,Transverse myelitis ,PRIMARY THROMBOSIS PREVENTION ,Rheumatology ,Lupus Vasculitis, Central Nervous System/diagnosis/etiology/psychology/*therapy ,Risk Factors ,Internal medicine ,MAGNETIC-RESONANCE SPECTROSCOPY ,medicine ,INTRAVENOUS IMMUNOGLOBULIN ,Humans ,Immunology and Allergy ,Optic neuritis ,Lupus vasculitis ,skin and connective tissue diseases ,Depression (differential diagnoses) ,Evidence-Based Medicine ,Systemic lupus erythematosus ,business.industry ,Mental Disorders ,CENTRAL-NERVOUS-SYSTEM ,Lupus Vasculitis, Central Nervous System ,Cranial Nerve Diseases/etiology ,Peripheral Nervous System Diseases ,ANTIPHOSPHOLIPID-ANTIBODY-SYNDROME ,Chorea ,Peripheral Nervous System Diseases/etiology ,medicine.disease ,Connective tissue disease ,central-nervous-system emission computed-tomography antiphospholipid-antibody-syndrome magnetic-resonance spectroscopy primary thrombosis prevention of-the-literature recurrent thrombosis risk-factors intravenous immunoglobulin cognitive dysfunction ,Cranial Nerve Diseases ,Peripheral neuropathy ,Mental Disorders/etiology ,OF-THE-LITERATURE ,Spinal Cord Diseases/etiology ,RISK-FACTORS ,medicine.symptom ,business - Abstract
ObjectivesTo develop recommendations for the diagnosis, prevention and treatment of neuropsychiatric systemic lupus erythematosus (NPSLE) manifestations.MethodsThe authors compiled questions on prevalence and risk factors, diagnosis and monitoring, therapy and prognosis of NPSLE. A systematic literature search was performed and evidence was categorised based on sample size and study design.ResultsSystemic lupus erythematosus (SLE) patients are at increased risk of several neuropsychiatric manifestations. Common (cumulative incidence >5%) manifestations include cerebrovascular disease (CVD) and seizures; relatively uncommon (1–5%) are severe cognitive dysfunction, major depression, acute confusional state (ACS), peripheral nervous disorders psychosis. Strong risk factors (at least fivefold increased risk) are previous or concurrent severe NPSLE (for cognitive dysfunction, seizures) and antiphospholipid antibodies (for CVD, seizures, chorea). The diagnostic work-up of suspected NPSLE is comparable to that in patients without SLE who present with the same manifestations, and aims to exclude causes unrelated to SLE. Investigations include cerebrospinal fluid analysis (to exclude central nervous system infection), EEG (to diagnose seizure disorder), neuropsychological tests (to assess cognitive dysfunction), nerve conduction studies (for peripheral neuropathy) and MRI (T1/T2, fluid-attenuating inversion recovery, diffusion-weighted imaging, enhanced T1 sequence). Glucocorticoids and immunosuppressive therapy are indicated when NPSLE is thought to reflect an inflammatory process (optic neuritis, transverse myelitis, peripheral neuropathy, refractory seizures, psychosis, ACS) and in the presence of generalised lupus activity. Antiplatelet/anticoagulation therapy is indicated when manifestations are related to antiphospholipid antibodies, particularly thrombotic CVD.ConclusionsNeuropsychiatric manifestations in SLE patients should be first evaluated and treated as in patients without SLE, and secondarily attributed to SLE and treated accordingly.
- Published
- 2010
17. Response to: ’Neuropsychiatric lupus or not? Cerebral hypoperfusion by perfusion-weighted MRI in normal-appearing white matter in primary neuropsychiatric lupus erythematosus' by Papadakiet al'by Wallace
- Author
-
Prodromos Sidiropoulos, Efrosini Papadaki, Panagiotis G. Simos, George Bertsias, Eleftherios Kavroulakis, Dimitra Karageorgou, Dimitrios T. Boumpas, and Antonis Fanouriakis
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Immunology ,General Biochemistry, Genetics and Molecular Biology ,White matter ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Perfusion Weighted MRI ,immune system diseases ,Internal medicine ,Humans ,Lupus Erythematosus, Systemic ,Immunology and Allergy ,Medicine ,Lupus vasculitis ,skin and connective tissue diseases ,030203 arthritis & rheumatology ,Systemic lupus erythematosus ,Lupus erythematosus ,medicine.diagnostic_test ,Cerebral hypoperfusion ,business.industry ,Lupus Vasculitis, Central Nervous System ,Magnetic resonance imaging ,medicine.disease ,Magnetic Resonance Imaging ,White Matter ,Dermatology ,030104 developmental biology ,medicine.anatomical_structure ,business - Abstract
We thank Dr Wallace1 for his interest in our paper entitled ‘Neuropsychiatric lupus or not? Cerebral hypoperfusion by perfusion-weighted MRI in normal appearing white matter in primary neuropsychiatric lupus erythematosus’ by Papadaki et al 2 and for giving us the opportunity to clarify aspects of our work. Our response to the points raised, follow next: 1. American College of Rheumatology ( ACR) nomenclature . We do agree that this nomenclature, although useful, is indeed outdated and may need refinement and updating. In our study, the attribution of primary NPSLE …
- Published
- 2018
18. A decade of mycophenolate mofetil for lupus nephritis: is the glass half-empty or half-full?
- Author
-
George Bertsias, James E. Balow, and Dimitrios T. Boumpas
- Subjects
Oncology ,medicine.medical_specialty ,Cyclophosphamide ,business.industry ,Immunology ,Lupus nephritis ,Azathioprine ,Pharmacology ,medicine.disease ,Connective tissue disease ,General Biochemistry, Genetics and Molecular Biology ,Mycophenolic acid ,Organ transplantation ,Rheumatology ,Maintenance therapy ,Internal medicine ,Toxicity ,medicine ,Immunology and Allergy ,business ,medicine.drug - Abstract
The treatment of proliferative lupus nephritis (LN) can be staged as a period of intensive immunosuppressive therapy aimed at halting immunological injury (induction therapy) followed by a period of less aggressive maintenance therapy to consolidate the response. Maintenance therapy should be continued into the period of disease quiescence to decrease the number of flares and renal damage accrual.1 Randomised controlled trials (RCTs) have shown that adjunctive immunosuppressive agents are more effective than glucocorticoids alone in protecting against the risk of progression to end-stage renal disease (ESRD). Long-term (>10 years) efficacy has been demonstrated only for cyclophosphamide (CY)-based regimens1,–,3; however, CY is associated with gonadal toxicity, which is both dose- and age-dependent.4 Mycophenolate mofetil (MMF), with little if any gonadal toxicity, has been examined as an alternative to CY for both induction and maintenance therapies. MMF has been shown in several RCTs to achieve comparable short-term rates of partial remission of LN, but it remains to be proved whether it will ultimately be as effective as CY in pre-empting ESRD. Irrespective of the choice of induction therapy, there is broad consensus that maintenance therapy must be well tolerated, reasonably affordable and have intrinsically low rates of toxicity. Currently, the two most common choices for maintenance therapy are MMF and azathioprine (AZA). These two agents have distinct but similar mechanisms of action as purine antimetabolites. There is ongoing controversy about the objective evidence for the superiority of MMF over AZA as maintenance therapy in organ transplantation as well as in other immune-mediated diseases.5 As a result, some have argued that the lack of objective superiority of MMF on organ survival does not justify the 16-fold higher cost of MMF over AZA, although it is expected to be reduced after the patent expires at …
- Published
- 2010
19. A2.8 Enhanced Neutrophil Extracellular Trap Formation in Rheumatoid Arthritis Patients is Correlated with High Levels of Rheumatoid Factor (RF)
- Author
-
Garyfalia Papadaki, Argyro Repa, George Bertsias, Prodromos Sidiropoulos, Panayotis Verginis, Ioannis Mitroulis, Dimitrios T. Boumpas, Christiana Choulaki, and Amalia Raptopoulou
- Subjects
biology ,business.industry ,Immunology ,Fluorescence spectrometry ,Arthritis ,Inflammation ,Neutrophil extracellular traps ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Rheumatology ,Rheumatoid arthritis ,Myeloperoxidase ,medicine ,biology.protein ,Immunology and Allergy ,Synovial fluid ,Rheumatoid factor ,medicine.symptom ,business - Abstract
Background/Objectives Neutrophils are the most abundant cell type identified in joints from patients with rheumatoid arthritis (RA), with a key role in inflammation and cartilage damage. Activated neutrophils form extracellular traps (NETs) with potent pro-inflammatory and immunostimulatory activity. Consequently, we sought to assess the role of NET release (NETosis) in RA pathogenesis and whether RA specific autoantibodies (rheumatoid factor [RF]) are correlated to this phenomenon. Materials/Methods Peripheral blood neutrophils were isolated from active RA patients (n = 6) (Disease activity score, DAS28 > 5.1) and healthy control subjects (n = 7). NET formation from neutrophils, both spontaneous and following incubation with RA serum (n = 7) or synovial fluid (n = 7), was assessed by immunofluoresence microscopy, using co-staining with myeloperoxidase and 4’,6-Diamidino-2-phenylindole dihydrochloride (DAPI). The percentage of NET releasing cells was determined by examining 200 cells per sample in a double blind fashion. Extracellular DNA content was quantified by fluorescence spectrometry (picogreen) and NET fold increase was calculated based on the extracellular DNA content produced by healthy unstimulated neutrophils. Results Freshly isolated neutrophils from the peripheral blood of RA patients underwent spontaneous NETosis at higher rates compared to healthy controls (12 ± 2.1% versus 3.2 ± 0.9%, p Conclusions We found that neutrophils from RA patients have enhanced NET formation, driven by soluble factors found in RA sera and synovial fluid, and this is associated with presence of RF. Further studies will address whether NETs are involved in the initiation of adaptive immune responses in humans and in mouse model of arthritis, and whether suppression of NETosis may ameliorate arthritis in RA mouse models.
- Published
- 2013
20. A5.26 Regulation of Expression and Function of Negative Immunomodulatory Receptors in B-Cells: Implications for the Pathogenesis of Systemic Lupus Erythematosus
- Author
-
Garyfalia Papadaki, Prodromos Sidiropoulos, George Bertsias, Irini Gergianaki, Amalia Zampoylaki, Dimitrios T. Boumpas, Christianna Choulaki, and Antonis Fanouriakis
- Subjects
CD86 ,medicine.medical_specialty ,business.industry ,Immunology ,BTLA ,Context (language use) ,Stimulation ,CHOP ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Lymphoma ,Endocrinology ,Rheumatology ,Internal medicine ,Immunology and Allergy ,Medicine ,business ,Receptor ,CD80 - Abstract
= 0.50, p
- Published
- 2013
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.