scholarly journals AB0305 STUDY OF CORRELATION OF B-CELL LEVEL AND PROGRESSION OF BONE DESTRUCTION IN PATIENTS WITH RHEUMATOID ARTHRITIS RECEIVING RITUXIMAB THERAPY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1451.1-1451
Author(s):  
A. Kudryavtseva ◽  
G. Lukina ◽  
A. Smirnov ◽  
S. Glukhova ◽  
E. Aronova ◽  
...  

Background:Rheumatoid arthritis is a chronic autoimmune disease characterised by inflammation of the synovial tissue and destruction of the underlying cartilage and bone. The goal of antirheumatic treatment is not only to attenuate the clinical symptoms of joint inflammation, but also to inhibit the progression of joint destruction. Rituximab - it is a chimeric monoclonal antibody that targets the CD20 molecule expressed on the surface of B cells. It has been successfully used to treat rheumatoid arthritis, and it is worth noting that his antidestructive effect sometimes does not meet the clinical.Objectives:The aim of our study was to evaluate the correlation between the degree of В-cell depletion and the development of the clinical and antidestructive effects of Rituximab (RTM) therapy in patients with rheumatoid arthritis (RA).Methods:the study included 108 patients (pts) with rheumatoid arthritis, most are middle-aged women with high disease activity (mean DAS28 6,1±1.04, RF-positive 77%, ACCP-positive 83%) treated with RTX (1000 mgx2 or 500 mgx2). Clinical effect was scored by EULAR criteria, radiographic progression was assessed using Sharp/van der Heijde (SvH) modified scoring method. B-cell level was measured with flow cytometry.Results:patients who were treated by different doses of RTX (500 x2 or 1000 x2) had good response. After 48 week of treatment RTX clinical improvement was achieved in 65% pts, good and moderate response by EULAR criteria in 23 % and 42 % pts respectively. Noteworthy, after 12 months of treatment RTX radiological progression was absent in 50 % pts with high disease activity. There was no significant difference in the degree of B-cell reduction when assessing the antidestructive effect. However, in assessing the clinical effect, it was noted that depletion of B cells in patients with RA in a state of remission (median 0.05% B cells) was more pronounced than in patients with signs of disease activity (2.03% B cells).Conclusion:rituximab therapy slows the radiologic progression regardless of the therapeutic effect. Radiologic progression did not show any dependence on the degree of B-cell reduction. The most pronounced depletion of B cells was observed in RA patients in a state of remission.Disclosure of Interests:Anastasia Kudryavtseva: None declared, Galina Lukina Speakers bureau: Novartis, Pfizer, UCB, Abbvie, Biocad, MSD, Roche, Alexander Smirnov: None declared, Svetlana Glukhova: None declared, Eugenia Aronova: None declared, Galina Gridneva: None declared

2011 ◽  
Vol 38 (11) ◽  
pp. 2301-2308 ◽  
Author(s):  
YING-QIAN MO ◽  
LIE DAI ◽  
DONG-HUI ZHENG ◽  
LANG-JING ZHU ◽  
XIU-NING WEI ◽  
...  

Objective.The efficacy of B cell depletion in the treatment of patients with rheumatoid arthritis (RA) has revitalized interest in the pathogenic role(s) of B cells in RA. We evaluated the distribution of synovial B lineage cells and their correlation with histologic disease activity and joint destruction in RA.Methods.Synovial tissue samples were obtained by closed-needle biopsy from 69 Chinese patients with active RA, from 14 patients with osteoarthritis (OA), and from 15 with orthopedic arthropathies (OrthA) as disease controls. Serial tissue sections were stained immunohistochemically for CD79a (pro-B cell to plasma cell), CD20 (B cells), CD38 (plasma cells), CD21 (follicular dendritic cells), CD68 (macrophages), CD3 (T cells), and CD34 (endothelial cells). Densities of positive-staining cells were determined and correlated with histologic disease activity (Krenn 3-component synovitis score) and radiographic joint destruction (Sharp score).Results.Mean sublining CD79a-positive cell density was significantly higher in RA than in OA (p <0.001) or OrthA (p = 0.003). Receiver operating characteristic curve analysis showed that CD79a-positive cell density differentiated RA well from OA [area under the curve (AUC) = 0.79] or OrthA (AUC = 0.75). Spearman’s rank order correlation showed significant correlations between sublining CD79a-positive cell density and the synovitis score (r = 0.714, p < 0.001), total Sharp score (r = 0.490, p < 0.001), and the erosion subscore (r = 0.545, p < 0.001), as well as the joint space narrowing subscore (r = 0.468, p = 0.001) in RA.Conclusion.Synovial CD79a-positive B cells may be a helpful biomarker for histologic disease activity in RA and may be involved in the pathogenesis of joint destruction in RA.


2010 ◽  
Vol 67 (4) ◽  
pp. 286-290 ◽  
Author(s):  
Aleksandra Tomic-Lucic ◽  
Suzana Pantovic ◽  
Gvozden Rosic ◽  
Zdravko Obradovic ◽  
Mirko Rosic

Background/Aim. Many arguments prove the pathophysiologic role of histamine in the process of remodeling and joint destruction in rheumatoid arthritis. The aim of our study was to find out if there was a relation between histamine concentration in synovial fluid and blood with clinical expression of disease activity. Methods. Histamine concentration in synovial fluid and blood was determinated in 19 patients with rheumatoid arthritis. Histamine concentration measurement was based on the Shore's fluorometric method. Histamine index (HI) was evaluated as a ratio between histamine concentration in synovial fluid and blood. Disease activity score, DAS 28 (3), with three variables (erythrocyte sedimentation rate, the number of swelled joints and the number of tender joints) was also evaluated. Results. Our results showed that there was no significant difference in concentration of histamine in synovial fluid and blood related to disease activity. However, there was a significant difference in the histamine index which was increased proportionally with disease activity. Conclusion. Our study indicates that histamine index could be useful in estimation of rheumatoid arthritis activity.


2018 ◽  
Vol 77 (12) ◽  
pp. 1773-1781 ◽  
Author(s):  
Felice Rivellese ◽  
Daniele Mauro ◽  
Alessandra Nerviani ◽  
Sara Pagani ◽  
Liliane Fossati-Jimack ◽  
...  

ObjectivesMast cells (MCs) are involved in the pathogenesis of rheumatoid arthritis (RA). However, their contribution remains controversial. To establish their role in RA, we analysed their presence in the synovium of treatment-naïve patients with early RA and their association and functional relationship with histological features of synovitis.MethodsSynovial tissue was obtained by ultrasound-guided biopsy from treatment-naïve patients with early RA (n=99). Immune cells (CD3/CD20/CD138/CD68) and their relationship with CD117+MCs in synovial tissue were analysed by immunohistochemistry (IHC) and immunofluorescence (IF). The functional involvement of MCs in ectopic lymphoid structures (ELS) was investigated in vitro, by coculturing MCs with naïve B cells and anticitrullinated protein antibodies (ACPA)-producing B cell clones, and in vivo in interleukin-27 receptor alpha (IL27ra)-deficient and control mice during antigen-induced arthritis (AIA).ResultsHigh synovial MC counts are associated with local and systemic inflammation, autoantibody positivity and high disease activity. IHC/IF showed that MCs reside at the outer border of lymphoid aggregates. Furthermore, human MCs promote the activation and differentiation of naïve B cells and induce the production of ACPA, mainly via contact-dependent interactions. In AIA, synovial MC numbers increase in IL27ra deficient mice, in association with ELS and worse disease activity.ConclusionsSynovial MCs identify early RA patients with a severe clinical form of synovitis characterised by the presence of ELS.


2010 ◽  
Vol 69 (12) ◽  
pp. 2181-2188 ◽  
Author(s):  
Inmaculada de la Torre ◽  
Rita A Moura ◽  
Maria J Leandro ◽  
Jonathan Edwards ◽  
Geraldine Cambridge

ObjectivesTo examine the expression of B-cell-activating factor receptor (BAFF-R) on naive CD27− and memory CD27+ B cells in normal individuals and patients with rheumatoid arthritis (RA) undergoing B-cell depletion therapy with rituximab.Patients and MethodsBAFF-R expression on B-cell subsets was determined in normal controls (NC; n=11), active patients with RA pre-rituximab (pre-RX; n=15), relapsing patients either concordant for B-cell repopulation (C-R, n=13) or discordant, with relapse more than 3 months after repopulation (D-R, n=11) and patients in remission over 3 months postrepopulation (discordant non-relapsing (D-NR), n=5). Serum BAFF was measured by ELISA and analysed using Mann–Whitney.ResultsThere was no significant difference between NC, pre-RX and D-NR patients in %BAFF-R-positive B cells or mean fluorescence intensity (MFI) in naive and memory B cells. Relapsing patients had significantly lower MFI and %BAFF-R-positive cells in both naive and memory compartments from NC and pre-RX (C-R and D-R; p<0.01). BAFF levels in pre-RX patients were within the normal range and did not correlate with BAFF-R expression in any patient group. D-NR patients had relatively lower proportions of pre and postswitch CD27+ B cells than pre-RX patients (D-NR vs pre-RX; p<0.05 for both) and also lower numbers of postswitch B cells than D-R patients (D-NR vs D-R, p<0.05).ConclusionBAFF-R expression was significantly reduced on both naive and memory B cells in patients at relapse, regardless of the relationship with B-cell repopulation or serum BAFF levels. Re-establishment of active disease was also associated with an increase in class-switch recombination. Factors responsible for lower levels of BAFF-R may relate to altered thresholds for autoreactive B-cell generation at relapse in patients with RA.


2019 ◽  
Vol 09 (01) ◽  
pp. e75-e83
Author(s):  
Hanan Aly Taha ◽  
Walaa G. Hozayen ◽  
Ahmed Mohamed Okasha ◽  
Amr E. Ahmed ◽  
Manar Ali A. Shata ◽  
...  

AbstractRheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by articular inflammation and joint destruction. The mechanism of RA pathogenesis is not fully understood, but humoral and cellular immunity are known to be involved. CD4+ T lymphocytes and cytokines released by these cells are suggested to initiate inflammation in RA. This study aimed to assess T helper 17 (Th17)/regulatory T (Treg) cell ratio and its correlation with disease activity in adult and juvenile RA. This study included 80 patients, with RA, including 40 adults (mean age: 36.4 ± 11.1 years and 40 juveniles mean age: 12.7 ± 2.2 years), and 80 healthy controls. For all patients and control subjects, patient and disease characteristics; laboratory tests for complete blood count, erythrocyte sedimentation rate, C-reactive protein (CRP), rheumatoid factor, anti-cyclic citrullinated peptide (anti-CCP), anti-nuclear antibodies (ANA), and flow cytometry to determine the numbers of Th17 and Treg cells. There was a statistically significant increase in the Th17/Treg ratio in patients with active disease compared with those with inactive disease for both adult and juvenile RA compared with controls. However, a similar significant difference was not observed between those with inactive adult and juvenile RA and controls. There were significant positive correlations between the Th17/Treg ratio and disease activity score 28 (DAS28), CRP, anti-CCP, and ANA in active adult and juvenile RA. The Th17/Treg ratio was increased in active form of adult and juvenile RA compared with inactive RA and control, indicating the Th17/Treg ratio as a potentially useful marker of disease activity.


2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Ying Zhang ◽  
Rong Cao ◽  
Haijian Ying ◽  
Juping Du ◽  
Shuaishuai Chen ◽  
...  

Toll-like receptor (TLR) 10, mainly expressed on B cells, has emerged as a modulatory receptor in inflammation. Nonetheless, the clinical significance of TLR10 in rheumatoid arthritis (RA) remains unclear. In this study, we explored the expression of TLR10 in B cells and B cell subsets in RA subjects and healthy controls (HCs) and determined its relevance to disease activity and inflammatory biomarkers. TLR10 levels in B cells and B cell subsets (CD19+CD27+, CD19+CD27−, CD27+IgD−, CD27+IgD+, CD27−IgD+, D27−IgD−, CD19+CD5+, and CD19+CD5−) and inflammatory biomarker concentrations in peripheral blood (PB) obtained from RA subjects and HCs were detected by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. The correlations of TLR10 expression with disease activity and inflammatory biomarkers were then analysed. Similar levels of TLR10 in all CD19+ B cells were observed in the RA subjects and HCs. Compared to that in the HCs, TLR10 was elevated significantly in the CD19+CD27−IgD− and CD19+CD5+ subsets in the RA subjects. In addition, almost all subsets expressing TLR10 were increased with disease activity. The present study reveals that enhanced TLR10 in B cell subsets is positively correlated with disease activity in RA subjects.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 477.2-477
Author(s):  
F. Hamdy ◽  
A. F. Enein ◽  
N. Morad ◽  
S. Tharwat ◽  
A. M. Abd el-Khalek ◽  
...  

Background:Rheumatoid arthritis (RA) is a systemic disease which results in chronic inflammation that primarily involves synovial joints resulting in progressive joint destruction [1]. Detection of subclinical disease activity is important as radiographic progression was observed during remission course in some cases [2]. Ultrasound can detect subclinical activity and synovial inflammation, which predict relapse and radiographic progression [3].Matrix Metaloprotinase 3 (MMP-3) is an enzyme, which is involved in joint destruction in RA patients. MMP-3 was found to correlate with disease activity, joint erosions, radiographic progression, drug responsiveness and disease outcome in patients with active RA [4]. However no data about its role in detection of subclinical activity in patients with clinical remission.Objectives:To assess the role of MMP-3 as a marker to discriminate subclinical activity from ultrasound remission in rheumatoid arthritis patients with remission.Methods:This study was conducted on 45 RA patients fulfilling remission or low disease activity criteria according to DAS 28 AND 45 healthy controls. Ultrasound evaluation was done for all patients using modified German US7 score. According to US7 score patients were classified into two groups: group with sonographic remission in which GS is 0±1 and the other group with subclinical disease activity with higher GS. Both groups underwent clinical and laboratory evaluation including MMP-3.Results:Sonographic remission was achieved in 44% of patients (20 patients). There was no statistically significant difference as regard age, gender, smoking, disease duration, morning stiffness duration, CDAI, treatment and laboratory data apart from hemoglobin level between patients with subclinical disease activity and patients with remission. However, there is statistically significant difference between the two groups as regard joint deformity, extra articular manifestations, DAS 28, SDAI and hemoglobin level.There was statistically significant difference in serum MMP-3 between RA patients and healthy control group. Serum MMP-3 was higher in RA patients with subclinical activity than patients with sonographic remission but the difference was not statistically significant (figure 1). Serum MMP-3 was positively correlated with ESR and synovitis score.Figure 1.Conclusion:Serum MMP-3 has correlation with US synovitis score. However, serum MMP-3 was not able to differentiate patients with sonographic remission from patients with subclinical disease activity. Ultrasound is still the gold standard for detection of subclinical disease activity.References:[1]Ergin, S. (2000). “Romatoid Artrit ve Sjögren Sendromu.” Fiziksel Tip ve Rehabilitasyon, Güneş Kitapevi: 1549-1576.[2]Ogishima, H., H. Tsuboi, N. Umeda, M. Horikoshi, Y. Kondo, M. Sugihara, T. Suzuki, I. Matsumoto and T. Sumida (2014). “Analysis of subclinical synovitis detected by ultrasonography and low-field magnetic resonance imaging in patients with rheumatoid arthritis.” Modern rheumatology24(1): 60-68.[3]Filippucci, E., E. Cipolletta, R. M. Mirza, M. Carotti, A. Giovagnoni, F. Salaffi, M. Tardella, A. Di Matteo and M. Di Carlo (2019). “Ultrasound imaging in rheumatoid arthritis.” La radiologia medica124(11): 1087-1100.[4]Lerner, A., S. Neidhöfer, S. Reuter and T. Matthias (2018). “MMP3 is a reliable marker for disease activity, radiological monitoring, disease outcome predictability, and therapeutic response in rheumatoid arthritis.” Best Practice & Research Clinical Rheumatology32(4): 550-562.Disclosure of Interests:None declared


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 424.1-424
Author(s):  
A. Navrátilová ◽  
L. Andres Cerezo ◽  
H. Hulejova ◽  
V. Becvar ◽  
D. Tegzová ◽  
...  

Background:Interleukin 40 (IL-40) is newly identified B cell - associated cytokine implicated in humoral immune responses and in B cell development. As B cells play a pivotal role in autoimmunity, we aimed to investigate the function of IL-40 in rheumatoid arthritis (RA).Objectives:The aim of our study was to determine the function of IL-40 in RA.Methods:IL-40 expression in the synovial tissue was determined by immunohistochemistry and immunofluorescence (n=4-5). IL-40 was analysed in the serum/synovial fluid of patients with RA (n=69), systemic lupus erythematosus (SLE; n=69), osteoarthritis (OA; n=44), and in healthy controls (HC; n=25). Given the association of IL-40 with B cells, we analysed the effect of rituximab therapy on the serum IL-40 in 19 patients with RA after 16 and 24 weeks of the therapy. The clinical activity of patients with RA was assessed according to the 28 joint count Disease Activity Score (DAS28). Levels of C-reactive protein (CRP) and autoantibodies were measured by routine laboratory techniques. In vitro experiments were performed in RA synovial fibroblasts (n=9). Levels of cytokines and inflammatory mediators were determined in serum, synovial fluid and supernatants using ELISA or multiplex immunoassay.Results:IL-40 was overexpressed in RA synovial tissue compared to OA, particularly by synovial fibroblasts and immune cells such as B and T lymphocytes, macrophages and neutrophils. The levels of IL-40 were significantly higher in the synovial fluid of RA patients compared to OA (33.2 (6.6-68.9) vs. 0.7 (0.1-2.4) ng/ml; p<0.0001). In addition, IL-40 was increased in the serum of RA patients compared to SLE, OA or HC (4.8 (1.7-24.9) vs. 1.4 (1.0-1.9), 1.6 (0.6-3.1) or 1.5 (0.7-2.7) ng/ml; p<0.0001 for all) and decreased after 16 (p<0.01) and 24 weeks (p<0.001) in a subgroup of rituximab treated patients with RA. IL-40 levels in RA patients correlated with autoantibodies rheumatoid factor (IgM) and anti-citrullinated protein antibody (ACPA) in the serum (p<0.0001 and p<0.01) as well as in the synovial fluid (p<0.0001 and p<0.001). IL-40 in RA synovial fluid was also significantly associated with DAS28 (p<0.05), synovial fluid leukocyte count (p<0.01), number of swollen joints (p<0.05) and neutrophil attractants IL-8 (p<0.01) and MIP-1α (p<0.01). RA synovial fibroblasts exposed to recombinant IL-40 increased secretion of IL-8 (p<0.01), MCP-1 (p<0.05) and MMP-13 (p<0.01) compared to unstimulated cells in in vitro conditions.Conclusion:Our results show for the first time that IL-40 is elevated in RA and decreases following B-cell depletion therapy. The association of IL-40 with autoantibodies and chemokines may imply its potential involvement in RA development. Moreover, IL-40 up-regulates the secretion of chemokines and MMP-13 by synovial fibroblasts, indicating its role in the regulation of inflammation and tissue destruction in RA.Acknowledgements:Supported by MHCR 023728 a SVV 260 523Disclosure of Interests:None declared


Author(s):  
Soniya Krishnan ◽  
Balan C. S. ◽  
Seema P. Mohamedali

Background: Rheumatoid Arthritis (RA) is a chronic disabling disorder that lowers quality of life in the affected patients. Early treatment with disease-modifying anti-rheumatic drugs (DMARDs, provides better control of disease and minimize joint destruction. Long term therapy imparts considerable economic burden to the patients. Cost effective analysis was performed among the patients treated with methotrexate (MTX) alone, hydroxychloroquine (HCQ) alone, and both (MTX+HCQ).Methods: A prospective, observational study for six months to analyze the cost-effectiveness in RA patients with DMARDs-MTX, HCQ and MTX+HCQ. A total of 91 patients were included for analysis; 43 patients in MTX and HCQ group; 37 patients in MTX group and 11 patients in HCQ group. To assess the functional disability,” Stanford Health Assessment Questionnaire - Disability Index” (HAQ-DI) was administered. The patients were followed up for four months. The HAQ-DI at the baseline was compared with that of final follow up. The change in HAQ-DI and the total costs were used to find out the average cost- effective ratio (ACER).Results: The least ACER was obtained for Hydroxychloroquine and highest was for Methotrexate. But there was no statistically significant difference in ACER between various treatment groups. There was no significant difference in the disease activity improvement between the three groups.Conclusions: MTX, HCQ and MTX+HCQ showed improvement in disease activity without any significant difference. MTX is superior considering direct cost but there is no difference in the total cost between three groups.


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