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AB0381 Expression of Toll-like Receptors and Distribution of Immune-Cells in Rheumatoid Synovial Tissues of The Patients Treated by Abatacept
  1. Y. Takakubo,
  2. Y. Naganuma,
  3. H. Oki,
  4. S. Yang,
  5. K. Sasaki,
  6. M. Takagi
  1. Department of Orthopaedic Surgery, Yamagata University Faculty of Medicine, Yamagata, Japan

Abstract

Background Rheumatoid arthritis (RA) is a progressive chronic autoimmune and autoinflammatory disease affecting multiple joints simultaneously1. Abatacept (ABT) which is cytotoxic T-lymphocyte-associated protein (CTLA) 4-Ig agent is one of biologics2.

Objectives The aim of this study is to examine the effect of ABT for evaluating immune-reactive cells with toll-like receptors in the synovial tissue samples of RA patients with ABT therapy (ABT groups) compared to them with non-biological therapy (Non-BIO groups).

Methods Synovial tissue samples of 20 RA (10 ABT and 10 Non-BIO samples) were immunohistochemically stained with TLR+ and immune-reactive cells including T cells (CD2), B cells (CD20), macrophage (CD68), conventional dendritic cells (cDC; S100, DC-LAMP), regulatory T cells (FoxP3) and indoleamine 2,3-dioxygenase+ cells (IDO). Positive cells were counted per 10 fields (x 200) by microscopy. TLR positive cells were analyzed by double Immunofluorescent methods with T cell, B cell, macrophage, cDC and plasmacytoid DC (pDC; CD123)-markers and IDO. Synovial inflammation was estimated by Krenn grading score.

Results ABT and non-BIO group was shown the similar grading scores (2.3 vs 2.0), DAS28CRP4 (5.1 vs 4.3) and CRP (1.3 vs 0.9). IDO+ and FoxP3+ cells, not CD3+, CD20+ and CD68+ cells were correlated significant with DAS28CRP (4) in lymphoid aggregation in ABT groups (p<0.01). TLR immunoreactivity was also confirmed in pDCs and IDO+ cells by immunofluorescent staining (Fig. 1).

Conclusions ABT was reported the similar remarkable effect with other biologics. We have already shown the residual inflammation of synovitis with TLR expressions in the RA patients who were received TNF-blockers3. TLR+ cells were observed with T cells and B cells related local inflammatory grading in ABT groups, however regulatory immune-cells might be increased and regulate inflammatory simultaneously. CTLA-4 and IDO was recently revealed the generation of osteoclast 4,5. IDO+ cells increased in synovial tissues of ABT group compared to no-BIO group. ABT may not only regulate the immunosuppression but also suppress the activation of osteoclast in RA.

  1. Klareskog L, et al: Lancet 2004; 363: 675–681,

  2. Sokolove J, ARD, 2015, [Epub ahead of print]

  3. Takakubo Y, et al: Clin Rheumatol, 2013; 32: 853–61,

  4. Bozec A, et al: SciTranMed, 2014; 7; 235:235ra60

  5. Schiff M, et al: ARD, 2014;73: 2174–7.

Acknowledgement We sincerely thank a lot to Ms. Eiko Saito for her skillful technical support in immunohistochemistry.

Disclosure of Interest None declared

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