scholarly journals AB0036 CHILDREN WITH EXTENDED OLIGOARTICULAR AND POLYARTICULAR JUVENILE IDIOPATHIC ARTHRITIS HAVE A CYTOKINE PATTERN FAVOURING B CELL ACTIVATION IN CIRCULATION

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1321.3-1321
Author(s):  
R. A. Moura ◽  
F. Oliveira-Ramos ◽  
C. Marques ◽  
A. Brito ◽  
R. L. Teixeira ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
B Cell ◽  
Cell Activation ◽  
Large Fraction ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
B Cell Activation ◽  
Serum Samples ◽  
Early Ra ◽  
Cytokine Pattern

Background:Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. The majority of polyarticular JIA (pJIA) and a large fraction of extended oligoarticular JIA (oJIA) patients fulfil classification criteria for rheumatoid arthritis (RA) in adulthood. B-cells play several important roles in RA pathogenesis, but it is still unclear if the pattern of B-cell involvement in pJIA and extended oJIA follows what has been described for adults with RA.Objectives:The main goal of this study was to determine the concentration of cytokines potentially relevant for B-cell activation in serum from children with pJIA and extended oJIA when compared to children with persistent oJIA, adult JIA, early and established RA.Methods:Serum samples were collected from children with extended oJIA (n=8), persistent oJIA (n=6), pJIA (n=6), adult JIA (n=8), untreated early RA (<1 year of disease duration, n=12), established RA patients treated with synthetic disease-modifying anti-rheumatic drugs (DMARDs) (n=10) and two groups of age- and sex-matched healthy donors (children, n=6 and adults, n=10). A proliferation-inducing ligand (APRIL), B-cell activating factor (BAFF), interleukin (IL)-6 and IL-21 serum levels were measured by enzyme-linked immunosorbent assay (ELISA).Results:Children with extended oJIA, early and established RA patients had significantly higher BAFF serum levels when compared to controls, but no significant differences were observed in children with persistent oJIA, pJIA and adult JIA when compared to all groups included. APRIL serum levels were significantly increased in early and established RA patients when compared to both controls and children with persistent oJIA. No significant differences were found in APRIL concentrations between children with JIA, adult JIA and controls. IL-6 serum levels were significantly increased in children with extended oJIA, pJIA, early and established RA when compared to controls, but no significant differences were found in children with persistent oJIA and adult JIA patients. IL-21 serum levels were significantly increased in early RA when compared to controls, but no significant differences were observed between any of the other groups included.Conclusion:The similarity in B-cell cytokine pattern found between extended oJIA, pJIA, early and established RA patients, contrarily to what was observed in persistent oJIA, suggests an early B-cell involvement in the pathogenesis of extended oJIA and pJIA as described for RA.Disclosure of Interests:None declared

scholarly journals Cytokine pattern in very early rheumatoid arthritis favours B cell activation and survival

2010 ◽  
Vol 8 (S1) ◽  
Author(s):  
R A Moura ◽  
R Cascão ◽  
I Perpétuo ◽  
H Canhão ◽  
E Vieira de Sousa ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cell ◽  
Early Rheumatoid Arthritis ◽  
Cell Activation ◽  
B Cell Activation ◽  
Cytokine Pattern

scholarly journals CXCL13 as biomarker for histological involvement in Sjögren’s syndrome

Rheumatology ◽  
2019 ◽  
Vol 59 (1) ◽  
pp. 165-170 ◽  
Author(s):  
Serena Colafrancesco ◽  
Roberta Priori ◽  
Charlotte G Smith ◽  
Antonina Minniti ◽  
Valentina Iannizzotto ◽  
...  
Keyword(s):  
B Cell ◽  
Disease Severity ◽  
Cell Activation ◽  
Serum Levels ◽  
Serum Marker ◽  
Queen Elizabeth Hospital ◽  
B Cell Activation ◽  
Autoantibody Production ◽  
Germinal Centres ◽  
University Of Rome

Abstract Objectives SS is an autoimmune condition characterized by systemic B-cell activation, autoantibody production and ectopic germinal centres’ formation within the salivary gland (SG). The extent of SG infiltrate has been proposed as a biomarker of disease severity. Plasma levels of CXCL13 correlate with germinal centres’ activity in animal models and disease severity in SS, suggesting its potential use as a surrogate serum marker to monitor local B-cell activation. The aim of this study was to evaluate the potential role of CXCL13 as a biomarker of SG pathology in two independent SS cohorts. Methods 109 patients with SS were recruited at Sapienza University of Rome (Italy) (n = 60), or at Queen Elizabeth Hospital in Birmingham and Barts Health NHS Trust in London (n = 49). Both sera and matched minor SG biopsy were available. Sicca (n = 57) and healthy subjects’ (n = 19) sera were used as control. Results CXCL13 serum level was higher in SS patients compared with controls. Correlations between its serum levels and a series of histomorphological parameters, including size of the aggregates and the presence germinal centres', were observed. Conclusion Our data foster the use of CXCL13 to monitor the extent of local pathology in SS and its validation in longitudinal clinical studies.

scholarly journals Frequency and syndrome specificity of antibodies to aquaporin-4 in neurological patients with rheumatic disorders

2011 ◽  
Vol 17 (9) ◽  
pp. 1067-1073 ◽  
Author(s):  
Sven Jarius ◽  
Christian Jacobi ◽  
Jerome de Seze ◽  
Helene Zephir ◽  
Friedemann Paul ◽  
...  
Keyword(s):  
B Cell ◽  
Rheumatic Diseases ◽  
Neuromyelitis Optica ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Transverse Myelitis ◽  
B Cell Activation ◽  
Serum Samples ◽  
Neurological Patients ◽  
Spectrum Disorders

Background: A new autoantibody (termed NMO-IgG, or AQP4-Ab) has recently been described in patients with neuromyelitis optica (NMO) and its formes frustes, longitudinally extensive transverse myelitis (LETM) and recurrent optic neuritis (rON). However, AQP4-Ab has been found also in patients with co-existing rheumatic diseases such as systemic lupus erythematosus (SLE) or Sjögren’s syndrome (SS), conditions which are characterized by broad, polyspecific B cell activation. Objectives: In this study, we aimed at evaluating the syndrome specificity and frequency of AQP4-Ab in patients with rheumatic diseases and neurological symptoms. Methods: For this purpose, serum samples from 109 neurological patients with established connective tissue disorders (CTD) ( n = 54), possible CTD ( n = 42), or vasculitis ( n = 13) were analysed for the presence of AQP4-Ab by a cell-based assay employing recombinant human AQP4. Results: AQP4-Ab was detectable in 31/40 (78%) patients with CTD and NMO spectrum disorders (median titre, 1:1000) but in none of the samples obtained from patients with CTD or vasculitis and neurological disorders other than NMO, LETM, or rON ( n = 69). Conclusion: The high syndrome specificity of the antibody for neuromyelitis optica spectrum disorders (NMOSDs) in patients with CTD supports the concept of AQP4-Ab being involved in the pathogenesis of these neurological conditions, and argues against AQP4-Ab simply being part of the polyclonal B cell activation generally associated with rheumatic diseases. Moreover, the finding that AQP4-Ab is present in patients with CTD and co-existing NMOSD with approximately the same frequency as in patients without CTD strengthens the case of CTD and AQP4-Ab positive NMOSD representing two co-existing yet distinct entities in the majority of patients.

scholarly journals Cytokine pattern in very early rheumatoid arthritis favours B-cell activation and survival

Rheumatology ◽  
2010 ◽  
Vol 50 (2) ◽  
pp. 278-282 ◽  
Author(s):  
R. A. Moura ◽  
R. Cascao ◽  
I. Perpetuo ◽  
H. Canhao ◽  
E. Vieira-Sousa ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cell ◽  
Early Rheumatoid Arthritis ◽  
Cell Activation ◽  
B Cell Activation ◽  
Cytokine Pattern

Abatacept Reduces Levels of Switched Memory B Cells, Autoantibodies, and Immunoglobulins in Patients with Rheumatoid Arthritis

2014 ◽  
Vol 41 (4) ◽  
pp. 666-672 ◽  
Author(s):  
Mirko Scarsi ◽  
Lucia Paolini ◽  
Doris Ricotta ◽  
Antonio Pedrini ◽  
Silvia Piantoni ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Cell Activation ◽  
Serum Levels ◽  
Memory B Cells ◽  
Cell Phenotype ◽  
B Cell Activation ◽  
Switch Memory

Objective.Abatacept (ABA) is a chimeric molecule, able to block the CD28-mediated costimulatory pathway. To evaluate the hypothesis that, through this mechanism of action, ABA may down-modulate the immune responses of B lymphocytes in rheumatoid arthritis (RA), we investigated the serum levels of immunoglobulins (Ig), free light chains (FLC), anticitrullinated protein antibodies (ACPA), and rheumatoid factor (RF), as well as the number of B lymphocytes differentiated into post-switch memory cells in patients treated with ABA.Methods.The serum levels of Ig, FLC, different ACPA, RF isotypes, and the B cell phenotype were longitudinally evaluated in 30 patients with RA treated with ABA.Results.At baseline, the proportion of total and post-switch memory B cells was lower in RA than in healthy individuals. After 6 months of ABA treatment we observed significant reductions of serum levels of IgG, IgA, and IgM, as well as FLC, with a normalization in many patients who had initially abnormal values. A significant reduction of the titers of IgG- and IgA-ACPA, as well as of IgM-, IgA-, and IgG-RF was also observed. A decrease of autoantibodies below the upper limits of normal values was found in 2 of 26 patients (8%) initially seropositive for IgG-ACPA, 1 of 14 (7%) for IgA-ACPA, 5 of 22 (23%) for IgM-RF, 7 of 22 (30%) for IgA-RF, and 5 of 16 (31%) for IgG-RF. After treatment, the proportion of circulating post-switch memory B cells was also further significantly decreased.Conclusion.ABA treatment in patients with RA can reduce signs of polyclonal B cell activation, inducing a trend toward normalization of serum levels of different classes of Ig and of FLC, decreasing titers of ACPA and RF, and percentages of post-switch memory B cells.

scholarly journals CD21lo/−CD27−IgM− Double-Negative B Cells Accumulate in the Joints of Patients With Antinuclear Antibody-Positive Juvenile Idiopathic Arthritis

2021 ◽  
Vol 9 ◽  
Author(s):  
Johannes Dirks ◽  
Jonas Fischer ◽  
Gabriele Haase ◽  
Annette Holl-Wieden ◽  
Christine Hofmann ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Cross Sectional Study ◽  
Double Negative ◽  
B Cell Differentiation ◽  
B Cell Activation ◽  
Cross Sectional ◽  
B Cell Subsets

Juvenile idiopathic arthritis (JIA) encompasses a heterogeneous group of diseases. The appearance of antinuclear antibodies (ANAs) in almost half of the patients suggests B cell dysregulation as a distinct pathomechanism in these patients. Additionally, ANAs were considered potential biomarkers encompassing a clinically homogenous subgroup of JIA patients. However, in ANA+ JIA patients, the site of dysregulated B cell activation as well as the B cell subsets involved in this process is still unknown. Hence, in this cross-sectional study, we aimed in an explorative approach at characterizing potential divergences in B cell differentiation in ANA+ JIA patients by assessing the distribution of peripheral blood (PB) and synovial fluid (SF) B cell subpopulations using flow cytometry. The frequency of transitional as well as switched-memory B cells was higher in PB of JIA patients than in healthy controls. There were no differences in the distribution of B cell subsets between ANA- and ANA+ patients in PB. However, the composition of SF B cells was different between ANA- and ANA+ patients with increased frequencies of CD21lo/−CD27−IgM− “double negative” (DN) B cells in the latter. DN B cells might be a characteristic subset expanding in the joints of ANA+ JIA patients and are potentially involved in the antinuclear immune response in these patients. The results of our explorative study might foster further research dissecting the pathogenesis of ANA+ JIA patients.

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