THU0102 DENDRITIC CELLS AS A PREDICTOR OF GOOD CLINICAL RESPONSE IN RHEUMATOID ARTHRITIS PATIENTS

Background:Dendritic cells (DCs) are known to contribute to the pathogenesis of rheumatoid arthritis (RA) through presentation of cartilage glycoprotein, production of proinflammatory cytokines and activation of Th1/Th17 responses. DCs are a heterogeneous population and can be divided into groups: myeloid (mDCs) and plasmacytoid (pDCs). DCs can induce both immune response and tolerance.Objectives:To investigate the subpopulations of peripheral blood DCs (myeloid and plasmacytoid) in patients with early RA as a predictor of responsibility to disease-modifying antirheumatic drugs (DMARDs) treatment.Methods:Fifty two patients with early RA (duration of the disease up to 12 months) were included in the study. All patients fullfield ACR/EULAR criteria (2010) and received methotrexate, leflunomide, sulfasalazine or their combination. Fifty five patients with osteoarthritis (OA) used as a control group. Analysis of the content of the B-lymphocytes, myeloid and plasmacytoid DCs was carried out by flow cytometry. B-lymphocytes, subtypes of peripheral blood DCs were characterized by the following phenotypes: myeloid DCs (CD3-CD14-CD19-HLA-DR + CD11c + CD123-), plasmacytoid DCs (CD3-CD14-CD19-HLA-DR + CD11c-CD123 +), B-lymphocytes (CD19 +). Analyses were performed before treatment and after 3 and 6 months.Results:Patients with early RA are characterized by significant evaluation of the population of myeloid DCs in comparison of patients with osteoarthritis (26.6% vs 23.5, p=0.0007). Furthermore, the difference was found in the number of cells with the phenotype B-lymphocytes: 5.4% vs 3%, p = 0.0005). No significant differences were observed in the number of plasmocytoid DCs. After 3 and 6 month of observation we detected reducing amount of myeloid DCs 26.6% vs 21.1% vs 18.4% respectively. Also we revealed reducing B-cells in treatment (5.4% vs 3 % vs 2%). Disease activity according to DAS28 droped to low (4.32 to3.06, p=0.03). We also revealed a reliable negative correlation between both the activity of the disease and the B- cells (rS=-0.4, p=0.05, n=52) and myeloid DCS (rS=-0.6, p=0.0004, n=52). A reducing of the immune cells during the DMARDS therapy suggests that they are an attractive marker for good clinical response to therapy.Conclusion:The data obtained confirm the determining role of myeloid DC and B lymphocytes in maintaining systemic inflammation in rheumatoid arthritis. In addition, these cells are a target of DMARDs therapy and a predictor of a good clinical response.Disclosure of Interests:None declared

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AB0023 DENDRITIC CELLS AS A PROMINENT MARKERS OF AUTOIMMUNE DISEASES

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2293 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1045.2-1045

Author(s):

M. Korolev ◽

Y. Kurochkina ◽

N. Banshhikova ◽

V. Omelchenko ◽

A. Akimova ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Dendritic Cells ◽

Autoimmune Diseases ◽

B Lymphocytes ◽

Peripheral Blood ◽

Group Analysis ◽

Control Group ◽

Hla Dr ◽

Asas Criteria ◽

Plasmacytoid Dcs

Background:Dendritic cells (DCs) are known to contribute to the pathogenesis of different autoimmune diseases. It is clear nowadays the role of DCs in rheumatoid arthritis (RA) but not well investigated in Axial spondylitis (AxSpA). DCs are a heterogeneous population and can be divided into groups: myeloid (mDCs) and plasmacytoid (pDCs). DCs can induce both immune response and tolerance.Objectives:To investigate the subpopulations of peripheral blood myeloid and plasmacytoid DCs in patients with early stage of RA (duration of illness up to 12 months) and AS.Methods:The study include sixty five patients with early forms of diseases including 55 patients with RA and 10 patients with AxSpA. Diagnosis RA was established according ACR/EULAR criteria (2010). Diagnosis AxSpA was established according ASAS criteria. All patients received conventional synthetic DMARDs. Thirty patients with osteoarthritis (OA) used as a control group. Analysis of the content of the B-lymphocytes, myeloid and plasmacytoid DCs was carried out by flow cytometry. B-lymphocytes, subtypes of peripheral blood DCs were characterized by the following phenotypes: myeloid DCs (CD3-CD14-CD19-HLA-DR + CD11c + CD123-), plasmacytoid DCs (CD3-CD14-CD19-HLA-DR + CD11c-CD123 +), B-lymphocytes (CD19 +). Analyses were performed before treatment and after 3 and 6 months.Results:Patients with early RA are characterized by significant evaluation of the population of myeloid DCs in comparison of patients with osteoarthritis (25.3% vs 21.5, p=0.005). Furthermore, the difference was found in the number of cells with the phenotype B-lymphocytes: 5.7% vs 3.1%, p = 0.0007). No significant differences were observed in the number of plasmocytoid DCs. After 3 and 6 month of observation we detected reducing amount of myeloid DCs 26.7% vs 20.1% vs 16.4% respectively. Disease activity according to DAS28 droped to low (4.32 to3.06, p=0.03). Patients with AxSpA are characterized a lower mDCs levels in compared with RA (19.3% vs 26.7, p=0.07). After 6 month of investigation we detected decreasing mDCs (19.3% to 14.2%, p=0.05). The percent of pDCs were constant and did not differ from the level of healthy donors.Conclusion:The data obtained indicate that early form of rheumatic diseases namely rheumatoid arthritis and axial spondylitis have the common features such as the dominance of mDCs and their decreasing in reduction of activity of disease.Disclosure of Interests:None declared

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Rituximab therapy reduces activated B cells in both the peripheral blood and bone marrow of patients with rheumatoid arthritis: depletion of memory B cells correlates with clinical response

Arthritis Research & Therapy ◽

10.1186/ar2798 ◽

2009 ◽

Vol 11 (4) ◽

pp. R131 ◽

Cited By ~ 66

Author(s):

Magda Nakou ◽

Georgios Katsikas ◽

Prodromos Sidiropoulos ◽

George Bertsias ◽

Eva Papadimitraki ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Bone Marrow ◽

B Cells ◽

Clinical Response ◽

Peripheral Blood ◽

Memory B Cells ◽

Activated B Cells

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Faculty Opinions recommendation of Rituximab therapy reduces activated B cells in both the peripheral blood and bone marrow of patients with rheumatoid arthritis: depletion of memory B cells correlates with clinical response.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.8862961.9409060 ◽

2011 ◽

Author(s):

Michael McDermott ◽

Ceara Walsh

Keyword(s):

Rheumatoid Arthritis ◽

Bone Marrow ◽

B Cells ◽

Clinical Response ◽

Peripheral Blood ◽

Memory B Cells ◽

Activated B Cells

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Regulation of rheumatoid factor production by peripheral blood and synovial fluid B cells in rheumatoid arthritis

Immunology Letters ◽

10.1016/s0165-2478(97)87700-0 ◽

1997 ◽

Vol 56 (1-3) ◽

pp. 216

Author(s):

C Reparon-Schuijt

Keyword(s):

Rheumatoid Arthritis ◽

B Cells ◽

Synovial Fluid ◽

Rheumatoid Factor ◽

Peripheral Blood ◽

Factor Production

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A SIMPLE METHOD FOR THE PURIFICATION OF HUMAN PERIPHERAL BLOOD ANTIGEN PRESENTING CELLS (DENDRITIC CELLS, MONOCYTES/MACROPHAGES, AND B LYMPHOCYTES)

Immunological Investigations ◽

10.1081/imm-120016243 ◽

2002 ◽

Vol 31 (3-4) ◽

pp. 233-245 ◽

Cited By ~ 11

Author(s):

Anne M. Delles ◽

Kate Rittenhouse-Olson ◽

Janet Morgan ◽

Allan R. Oseroff

Keyword(s):

Dendritic Cells ◽

B Lymphocytes ◽

Peripheral Blood ◽

Human Peripheral Blood ◽

Antigen Presenting Cells ◽

Simple Method ◽

Antigen Presenting

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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.

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Interleukin-13 in Combination With CD40 Ligand Potently Inhibits Apoptosis in Human B Lymphocytes: Upregulation of Bcl-xL and Mcl-1

Blood ◽

10.1182/blood.v89.12.4415 ◽

1997 ◽

Vol 89 (12) ◽

pp. 4415-4424 ◽

Cited By ~ 54

Author(s):

Jon Lømo ◽

Heidi Kiil Blomhoff ◽

Sten Eirik Jacobsen ◽

Stanislaw Krajewski ◽

John C. Reed ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

B Lymphocytes ◽

Peripheral Blood ◽

Cell Apoptosis ◽

Cell Types ◽

Cd40 Ligand ◽

Interleukin 13

Abstract Interleukin-13 (IL-13) is a novel T-cell–derived cytokine with IL-4–like effects on many cell types. In human B lymphocytes, IL-13 induces activation, stimulates proliferation in combination with anti-IgM or anti-CD40 antibodies, and directs Ig isotype switching towards IgE and IgG4 isotypes. We show here that IL-13 also regulates human B-cell apoptosis. IL-13 reduced spontaneous apoptosis of peripheral blood B cells in vitro, as shown by measurement of DNA fragmentation using the TUNEL and Nicoletti assays. The inhibition of cell death by IL-13 alone was significant but modest, but was potently enhanced in combination with CD40 ligand (CD40L), a survival stimulus for B cells by itself. Interestingly, IL-13 increased the expression of CD40 on peripheral blood B cells, providing a possible mechanism for the observed synergy. IL-13 alone was a less potent inhibitor of apoptosis than IL-4. Moreover, there was no additive effect of combining IL-4 and IL-13 at supraoptimal concentrations, which is consistent with the notion that the IL-4 and IL-13 binding sites share a common signaling subunit. The combination of IL-13 with CD40L augmented the expression of the Bcl-2 homologues Bcl-xL and Mcl-1, suggesting this as a possible intracellular mechanism of induced survival. By contrast, levels of Bcl-2, and two other Bcl-2 family members, Bax and Bak, remained unaltered. Given the importance of the CD40-CD40L interaction in B-cell responses, these results suggest a significant role of IL-13 in the regulation of B-cell apoptosis.

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Normal mortality of the COBRA early rheumatoid arthritis trial cohort after 23 years of follow-up

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2018-214618 ◽

2019 ◽

Vol 78 (5) ◽

pp. 586-589 ◽

Cited By ~ 16

Author(s):

Pomme BM Poppelaars ◽

Lilian H D van Tuyl ◽

Maarten Boers

Keyword(s):

Rheumatoid Arthritis ◽

General Population ◽

Cox Regression ◽

Prospective Trial ◽

Reference Sample ◽

Health Assessment ◽

Early Ra ◽

Hla Dr ◽

Mortality Ratio

ObjectivesMortality in patients with rheumatoid arthritis (RA) is higher than in the general population. We investigated mortality in the COBRA-trial cohort after 23 years follow-up, compared with a reference sample of the Dutch population.MethodsThe COBRA-trial randomised patients with early RA to sulfasalazine monotherapy (SSZ, n=79) or a combination of SSZ, low-dose methotrexate and initially high, step-down prednisolone (COBRA, n=76). We compared the mortality in the COBRA-trial up to 2017 to a reference sample of the general population in the Netherlands (standardised mortality ratio, SMR), and its relation to early prognostic factors through stepwise Cox regression.ResultsDuration of follow-up in patients alive was mean 23 (range 22–24) years. In total, 44 patients died (28%, SMR=0.80 [95% CI 0.59 to 1.06]); 20 of 75 COBRA patients (27%, SMR 0.75 [0.47 to 1.14]) and 24 of 79 SSZ patients (30%, SMR 0.85 [0.56 to 1.25]); p=0.61). In the reference sample of the general population, 55 people (36%) died. 5 factors were significantly associated with increased mortality hazard: damage progression at 28 weeks; high Health Assessment Questionnaire (HAQ) score and absence of HLA-DR 2 or 3; disease duration from start of complaints was also significant, but showed an uninterpretable pattern.ConclusionsThis prospective trial cohort study of early RA is one of the first to show similar mortality compared with the general population after 23 years of follow-up. It confirms that early, intensive treatment of RA has long-term benefits and suggests that treating to target is especially important for patients with poor prognosis.

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