Increased Expression of TLR10 in B Cell Subsets Correlates with Disease Activity in Rheumatoid Arthritis

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.

Download Full-text

OP0005 ELEVATED STAT1 EXPRESSION BUT NOT PHOSPHORYLATION IN LUPUS B CELLS CORRELATES WITH DISEASE ACTIVITY AND INCREASED PLASMABLAST SUSCEPTIBILITY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2955 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 4-5

Author(s):

A. Aue ◽

F. Szelinski ◽

S. Weißenberg ◽

A. Wiedemann ◽

T. Rose ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

B Cells ◽

Autoimmune Diseases ◽

Disease Activity ◽

B Cell ◽

Lupus Erythematosus ◽

Type I ◽

Type I Ifn ◽

Systemic Lupus ◽

B Cell Subsets

Background:Systemic lupus erythematosus (SLE) is characterized by two pathogenic key signatures, type I interferon (IFN) (1.) and B-cell abnormalities (2.). How these signatures are interrelated is not known. Type I-II IFN trigger activation of Janus kinase (JAK) – signal transducer and activator of transcription (STAT).Objectives:JAK-STAT inhibition is an attractive therapeutic possibility for SLE (3.). We assess STAT1 and STAT3 expression and phosphorylation at baseline and after IFN type I and II stimulation in B-cell subpopulations of SLE patients compared to other autoimmune diseases and healthy controls (HD) and related it to disease activity.Methods:Expression of STAT1, pSTAT1, STAT3 and pSTAT3 in B and T-cells of 21 HD, 10 rheumatoid arthritis (RA), 7 primary Sjögren’s (pSS) and 22 SLE patients was analyzed by flow cytometry. STAT1 and STAT3 expression and phosphorylation in PBMCs of SLE patients and HD after IFNα and IFNγ incubation were further investigated.Results:SLE patients showed substantially higher STAT1 but not pSTAT1 in B and T-cell subsets. Increased STAT1 expression in B cell subsets correlated significantly with SLEDAI and Siglec-1 on monocytes, a type I IFN marker (4.). STAT1 activation in plasmablasts was IFNα dependent while monocytes exhibited dependence on IFNγ.Figure 1.Significantly increased expression of STAT1 by SLE B cells(A) Representative histograms of baseline expression of STAT1, pSTAT1, STAT3 and pSTAT3 in CD19+ B cells of SLE patients (orange), HD (black) and isotype controls (grey). (B) Baseline expression of STAT1 and pSTAT1 or (C) STAT3 and pSTAT3 in CD20+CD27-, CD20+CD27+ and CD20lowCD27high B-lineage cells from SLE (orange) patients compared to those from HD (black). Mann Whitney test; ****p≤0.0001.Figure 2.Correlation of STAT1 expression by SLE B cells correlates with type I IFN signature (Siglec-1, CD169) and clinical activity (SLEDAI).Correlation of STAT1 expression in CD20+CD27- näive (p<0.0001, r=0.8766), CD20+CD27+ memory (p<0.0001, r=0.8556) and CD20lowCD27high (p<0.0001, r=0.9396) B cells from SLE patients with (A) Siglec-1 (CD169) expression on CD14+ cells as parameter of type I IFN signature and (B) lupus disease activity (SLEDAI score). Spearman rank coefficient (r) was calculated to identify correlations between these parameters. *p≤0.05, **p≤0.01. (C) STAT1 expression in B cell subsets of a previously undiagnosed, active SLE patient who was subsequently treated with two dosages of prednisolone and reanalyzed.Conclusion:Enhanced expression of STAT1 by B-cells candidates as key node of two immunopathogenic signatures (type I IFN and B-cells) related to important immunopathogenic pathways and lupus activity. We show that STAT1 is activated upon IFNα exposure in SLE plasmablasts. Thus, Jak inhibitors, targeting JAK-STAT pathways, hold promise to block STAT1 expression and control plasmablast induction in SLE.References:[1]Baechler EC, Batliwalla FM, Karypis G, Gaffney PM, Ortmann WA, Espe KJ, et al. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci U S A. 2003;100(5):2610-5.[2]Lino AC, Dorner T, Bar-Or A, Fillatreau S. Cytokine-producing B cells: a translational view on their roles in human and mouse autoimmune diseases. Immunol Rev. 2016;269(1):130-44.[3]Dorner T, Lipsky PE. Beyond pan-B-cell-directed therapy - new avenues and insights into the pathogenesis of SLE. Nat Rev Rheumatol. 2016;12(11):645-57.[4]Biesen R, Demir C, Barkhudarova F, Grun JR, Steinbrich-Zollner M, Backhaus M, et al. Sialic acid-binding Ig-like lectin 1 expression in inflammatory and resident monocytes is a potential biomarker for monitoring disease activity and success of therapy in systemic lupus erythematosus. Arthritis Rheum. 2008;58(4):1136-45.Disclosure of Interests:Arman Aue: None declared, Franziska Szelinski: None declared, Sarah Weißenberg: None declared, Annika Wiedemann: None declared, Thomas Rose: None declared, Andreia Lino: None declared, Thomas Dörner Grant/research support from: Janssen, Novartis, Roche, UCB, Consultant of: Abbvie, Celgene, Eli Lilly, Roche, Janssen, EMD, Speakers bureau: Eli Lilly, Roche, Samsung, Janssen

Download Full-text

The expansion of activated naive DNA autoreactive B cells and its association with disease activity in systemic lupus erythematosus patients

Arthritis Research & Therapy ◽

10.1186/s13075-021-02557-0 ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Kittikorn Wangriatisak ◽

Chokchai Thanadetsuntorn ◽

Thamonwan Krittayapoositpot ◽

Chaniya Leepiyasakulchai ◽

Thanitta Suangtamai ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

B Cells ◽

Disease Activity ◽

B Cell ◽

Lupus Erythematosus ◽

Systemic Lupus ◽

Autoreactive B Cells ◽

Dsdna Antibody ◽

Cell Subpopulations ◽

B Cell Subsets

Abstract Background Autoreactive B cells are well recognized as key participants in the pathogenesis of systemic lupus erythematosus (SLE). However, elucidating the particular subset of B cells in producing anti-dsDNA antibodies is limited due to their B cell heterogeneity. This study aimed to identify peripheral B cell subpopulations that display autoreactivity to DNA and contribute to lupus pathogenesis. Methods Flow cytometry was used to detect total B cell subsets (n = 20) and DNA autoreactive B cells (n = 15) in SLE patients’ peripheral blood. Clinical disease activities were assessed in SLE patients using modified SLEDAI-2 K and used for correlation analyses with expanded B cell subsets and DNA autoreactive B cells. Results The increases of circulating double negative 2 (DN2) and activated naïve (aNAV) B cells were significantly observed in SLE patients. Expanded B cell subsets and DNA autoreactive B cells represented a high proportion of aNAV B cells with overexpression of CD69 and CD86. The frequencies of aNAV B cells in total B cell populations were significantly correlated with modified SLEDAI-2 K scores. Further analysis showed that expansion of aNAV DNA autoreactive B cells was more related to disease activity and serum anti-dsDNA antibody levels than to total aNAV B cells. Conclusion Our study demonstrated an expansion of aNAV B cells in SLE patients. The association between the frequency of aNAV B cells and disease activity patients suggested that these expanded B cells may play a role in SLE pathogenesis.

Download Full-text

Synovial Infiltration with CD79a-positive B Cells, But Not Other B Cell Lineage Markers, Correlates with Joint Destruction in Rheumatoid Arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.110615 ◽

2011 ◽

Vol 38 (11) ◽

pp. 2301-2308 ◽

Cited By ~ 16

Author(s):

YING-QIAN MO ◽

LIE DAI ◽

DONG-HUI ZHENG ◽

LANG-JING ZHU ◽

XIU-NING WEI ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

B Cells ◽

Disease Activity ◽

B Cell ◽

Cell Density ◽

Joint Destruction ◽

Chinese Patients ◽

Positive Staining ◽

Synovitis Score ◽

Sharp Score

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.

Download Full-text

SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00749-3 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Yukai Jing ◽

Li Luo ◽

Ying Chen ◽

Lisa S. Westerberg ◽

Peng Zhou ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Immune Regulation ◽

Cell Metabolism ◽

Healthy Controls ◽

Bcr Signaling ◽

Before And After ◽

B Cell Subsets ◽

Almost All ◽

Cd19 Expression

AbstractThe SARS-CoV-2 infection causes severe immune disruption. However, it is unclear if disrupted immune regulation still exists and pertains in recovered COVID-19 patients. In our study, we have characterized the immune phenotype of B cells from 15 recovered COVID-19 patients, and found that healthy controls and recovered patients had similar B-cell populations before and after BCR stimulation, but the frequencies of PBC in patients were significantly increased when compared to healthy controls before stimulation. However, the percentage of unswitched memory B cells was decreased in recovered patients but not changed in healthy controls upon BCR stimulation. Interestingly, we found that CD19 expression was significantly reduced in almost all the B-cell subsets in recovered patients. Moreover, the BCR signaling and early B-cell response were disrupted upon BCR stimulation. Mechanistically, we found that the reduced CD19 expression was caused by the dysregulation of cell metabolism. In conclusion, we found that SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism, which may provide a new intervention target to cure COVID-19.

Download Full-text

Mast cells in early rheumatoid arthritis associate with disease severity and support B cell autoantibody production

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2018-213418 ◽

2018 ◽

Vol 77 (12) ◽

pp. 1773-1781 ◽

Cited By ~ 20

Author(s):

Felice Rivellese ◽

Daniele Mauro ◽

Alessandra Nerviani ◽

Sara Pagani ◽

Liliane Fossati-Jimack ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

B Cells ◽

Mast Cells ◽

Disease Activity ◽

B Cell ◽

Synovial Tissue ◽

Autoantibody Production ◽

Early Ra ◽

Treatment Naïve

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.

Download Full-text

Elevated STAT1 expression but not phosphorylation in lupus B cells correlates with disease activity and increased plasmablast susceptibility

Rheumatology ◽

10.1093/rheumatology/keaa187 ◽

2020 ◽

Vol 59 (11) ◽

pp. 3435-3442 ◽

Cited By ~ 2

Author(s):

Arman Aue ◽

Franziska Szelinski ◽

Sarah Y Weißenberg ◽

Annika Wiedemann ◽

Thomas Rose ◽

...

Keyword(s):

B Cells ◽

Disease Activity ◽

B Cell ◽

Mononuclear Cells ◽

Janus Kinase ◽

T Cell Subsets ◽

Type I ◽

Type I Ifn ◽

Peripheral Blood Mononuclear ◽

B Cell Subsets

Abstract Objectives SLE is characterized by two pathogenic key signatures, type I IFN and B-cell abnormalities. How these signatures are interrelated is not known. Type I-II IFN trigger activation of Janus kinase (JAK) – signal transducer and activator of transcription (STAT). JAK-STAT inhibition is an attractive therapeutic possibility for SLE. We assess STAT1 and STAT3 expression and phosphorylation at baseline and after IFN type I and II stimulation in B-cell subpopulations of SLE patients compared with other autoimmune diseases and healthy controls (HD) and related it to disease activity. Methods Expression of STAT1, pSTAT1, STAT3 and pSTAT3 in B and T cells of 21 HD, 10 rheumatoid arthritis (RA), seven primary Sjögren’s (pSS) and 22 SLE patients was analysed by flow cytometry. STAT1 and STAT3 expression and phosphorylation in PBMCs (peripheral blood mononuclear cells) of SLE patients and HD after IFNα and IFNγ incubation were further investigated. Results SLE patients showed substantially higher STAT1 but not pSTAT1 in B- and T-cell subsets. Increased STAT1 expression in B-cell subsets correlated significantly with SLEDAI and Siglec-1 on monocytes, a type I IFN marker. STAT1 activation in plasmablasts was IFNα dependent while monocytes exhibited dependence on IFNγ. Conclusion Enhanced expression of STAT1 by B-cell candidates as a key node of two immunopathogenic signatures (type I IFN and B-cells) related to important immunopathogenic pathways and lupus activity. We show that STAT1 is activated upon IFNα exposure in SLE plasmablasts. Thus, Jak inhibitors, targeting JAK-STAT pathways, hold a promise to block STAT1 expression and control plasmablast induction in SLE.

Download Full-text

Remission Induced by TNF Inhibitors Plus Methotrexate is Associated With Changes in Peripheral Naïve B Cells in Patients With Rheumatoid Arthritis

Frontiers in Medicine ◽

10.3389/fmed.2021.683990 ◽

2021 ◽

Vol 8 ◽

Author(s):

Borja Hernández-Breijo ◽

Chamaida Plasencia-Rodríguez ◽

Victoria Navarro-Compán ◽

Carlota García-Hoz ◽

Israel Nieto-Gañán ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

B Cells ◽

B Cell ◽

Mononuclear Cells ◽

Tnf Inhibitors ◽

Concomitant Therapy ◽

Peripheral Blood Mononuclear ◽

Logistic Regression Models ◽

Cell Percentage ◽

B Cell Subsets

Biological therapies, such as TNF inhibitors (TNFi), are increasing remission (REM) rates in rheumatoid arthritis (RA) patients, although these are still limited. The aim of our study was to analyze changes in the profile of peripheral blood mononuclear cells (PBMC) in patients with RA treated with TNFi in relation to the clinical response. This is a prospective and observational study including 78 RA patients starting the first TNFi. PBMC were analyzed by flow cytometry both at baseline and at 6 months. Disease activity at the same time points was assessed by DAS28, establishing DAS28 ≤ 2.6 as the criteria for REM. Logistic regression models were employed to analyze the association between the changes in PBMC and REM. After 6 months of TNFi treatment, 37% patients achieved REM by DAS28. Patients who achieved REM showed a reduction in the percentage of naive B cells, but only when patients had received concomitant methotrexate (MTX) (OR: 0.59; 95% CI: 0.39–0.91). However, no association was found for patients who did not receive concomitant MTX (OR: 0.85; 95% CI: 0.63–1.16). In conclusion, PBMC, mainly the B-cell subsets, are modified in RA patients with TNFi who achieve clinical REM. A significant decrease in naive B-cell percentage is associated with achieving REM after 6 months of TNFi treatment in patients who received concomitant therapy with MTX.

Download Full-text

Imbalanced Immune Response of T-Cell and B-Cell Subsets in Patients with Moderate and Severe COVID-19

Viruses ◽

10.3390/v13101966 ◽

2021 ◽

Vol 13 (10) ◽

pp. 1966

Author(s):

Alexey Golovkin ◽

Olga Kalinina ◽

Vadim Bezrukikh ◽

Arthur Aquino ◽

Ekaterina Zaikova ◽

...

Keyword(s):

Immune Response ◽

B Cells ◽

B Cell ◽

Respiratory Rate ◽

Humoral Immune ◽

Tfh Cells ◽

Healthy Donors ◽

Immunological Changes ◽

B Cell Subsets ◽

Almost All

Background: The immunological changes associated with COVID-19 are largely unknown. Methods: Patients with COVID-19 showing moderate (n = 18; SpO2 > 93%, respiratory rate > 22 per minute, CRP > 10 mg/L) and severe (n = 23; SpO2 < 93%, respiratory rate >30 per minute, PaO2/FiO2 ≤ 300 mmHg, permanent oxygen therapy, qSOFA > 2) infection, and 37 healthy donors (HD) were enrolled. Circulating T- and B-cell subsets were analyzed by flow cytometry. Results: CD4+Th cells were skewed toward Th2-like phenotypes within CD45RA+CD62L− (CM) and CD45RA–CD62L− (EM) cells in patients with severe COVID-19, while CM CCR6+ Th17-like cells were decreased if compared with HD. Within CM Th17-like cells “classical” Th17-like cells were increased and Th17.1-like cells were decreased in severe COVID-19 cases. Circulating CM follicular Th-like (Tfh) cells were decreased in all COVID-19 patients, and Tfh17-like cells represented the most predominant subset in severe COVID-19 cases. Both groups of patients showed increased levels of IgD-CD38++ B cells, while the levels of IgD+CD38− and IgD–CD38− were decreased. The frequency of IgD+CD27+ and IgD–CD27+ B cells was significantly reduced in severe COVID-19 cases. Conclusions: We showed an imbalance within almost all circulating memory Th subsets during acute COVID-19 and showed that altered Tfh polarization led to a dysregulated humoral immune response.

Download Full-text

Beyond autoantibodies: Biological roles of human autoreactive B cells in rheumatoid arthritis revealed by whole transcriptome profiling

10.1101/144121 ◽

2017 ◽

Author(s):

Ankit Mahendra ◽

Xingyu Yang ◽

Shaza Abnouf ◽

Daechan Park ◽

Sanam Soomro ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

B Cells ◽

B Cell ◽

Cell Activation ◽

Transcriptome Profiling ◽

B Cell Activation ◽

Autoreactive B Cells ◽

Downstream Signaling ◽

Approved Drugs ◽

B Cell Subsets

AbstractAlthough the contribution of B-cell derived autoreactive antibodies to rheumatoid arthritis (RA) has been studied extensively, the autoantibody-independent roles of B cells in the progression of the disease is not well-defined. Here we present the first comprehensive transcriptome profile of human autoreactive B cells in an autoimmune disease by performing RNA-sequencing of citrulline-specific B cells from RA patients. In order to facilitate a comprehensive understanding of the profile of these citrulline-specific (RA-CCPPOS) B cells, we performed comparative analyses to both citrulline-negative (RA-CCPNEG) B cells from the same donors, and identified 431 differentially expressed genes (DEGs); and hemagglutinin-specific (HA) B cells from healthy individuals and identified 1658 DEGs. Three-way comparisons of these B cell populations demonstrated that RA-CCPPOS B cells, in comparison to the RA-CCPNEG B cells, demonstrate a potential role in protein citrullination and inflammation; RA-CCPPOS B cells in comparison to HA-specific B cells demonstrate RA-specific signatures like the expression of pro-inflammatory cytokines, chemokines, costimulatory molecules and B-cell activation cascades; and all B cells from RA patients demonstrated a significant impact of the multitude of TNF signaling pathways. Furthermore, transcription factor profiling suggested that cyclic AMP (cAMP) related pathways and downstream signaling molecules are selectively enriched in RA-CCPPOS cells in comparison to the other two B cell subsets. We advanced the understanding of the citrulline reactive B cells in RA pathophysiology by documenting and validating two novel observations in independent cohorts of patients: (1) the expression of IL15Rα is restricted to citrulline-specific cells within RA patients and the concentration of soluble IL15Rα is elevated in the sera of RA patients, (2) B cells from RA patients are capable of producing epidermal growth factor ligand, amphiregulin (AREG) which in turn has a direct impact on the mechanistic effectors of RA, osteoclasts and fibroblastlike synoviocytes (FLS). Overall, our comprehensive dataset identifies several existing FDA-approved drugs that can potentially be repurposed for RA and can serve as a foundation for studying the multi-faceted roles of B cells in other autoimmune diseases.

Download Full-text

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

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5638 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1451.1-1451

Author(s):

A. Kudryavtseva ◽

G. Lukina ◽

A. Smirnov ◽

S. Glukhova ◽

E. Aronova ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

B Cells ◽

Disease Activity ◽

B Cell ◽

Clinical Effect ◽

Joint Destruction ◽

High Disease Activity ◽

Cell Level ◽

Significant Difference ◽

Radiologic Progression

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

Download Full-text