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SAT0239 T Cell CD80/Cd86 Co-Stimulatory Blockade Effectively Suppresses CD25 (+) in CD4 (+) T Cell Subpopulation but not the ACPA Titers in the Course of 48-Week Treatment of Patients with Rheumatoid Arthritis
  1. M. Murakami1,2,
  2. M.N. Ito1,2,
  3. M. Sekiguchi3,
  4. K. Matsui3,
  5. M. Kitano3,
  6. Y. Imura4,
  7. K. Ohmura4,
  8. T. Fujii4,
  9. T. Kuroiwa5,
  10. K. Maeda6,
  11. S. Morita4,
  12. Y. Kawahito7,
  13. T. Mimori4,
  14. H. Sano3,
  15. N. Nishimoto1,2
  16. on behalf of ABROAD Study Group
  1. 1Tokyo Medical University
  2. 2Osaka Rheumatology Clinic, Osaka
  3. 3Hyogo College of Medicine, Hyogo
  4. 4Kyoto University, Kyoto
  5. 5Yukioka Hospital
  6. 6NTT West Osaka Hospital, Osaka
  7. 7Kyoto Prefectural University of Medicine, Kyoto, Japan

Abstract

Background Rheumatoid arthritis (RA) is a common immflamatory autoimmune disease characterized by persistent synovitis and progressive destruction of cartilage and bone in multiple joints. Among the autoantibodies detected in RA patients, circulating autoantibodies, anti-citrullinated protein/peptide antibodies (ACPA), are highly specific and useful diagnostic tools for RA. ACPA production seems to depend on antigen-specific CD4 (+) helper T cell activation. Activation of T cells requires costimulatory signals via binding of CD28 receptor with CD80/CD86 located on antigen-presenting cells (APC). Abatacept (ABA) is a biological agent for RA treatment, consisting of extracellular domains from cytotoxic T-lymphocyte antigen-4 and the Fc portion of human immunoglobulin G1 (CTLA-4-Ig) which competes with CD28 for CD80/86 binding.

Objectives This study aims to clarify how 48-week ABA treatment affects CD4 (+) T cell activation and ACPA production in RA patients.

Methods Peripheral blood mononucleated cells (PBMCs) and plasma were obtained from 30 patients enrolled in abatacept research outcome as a first-line biological agent in the real world (ABROAD study) at baseline, 24 and 48 weeks of ABA treatment. Fifty-three healthy individuals (HIs) were also enrolled as controls. Surface phenotypes and activation markers of T cells were analyzed with flow cytometory. ACPA titers were measured with EliA CCP ELISA kit.

Results Twenty-five patients (83.3%) were ACPA (+) (>4.5 U/mL). DAS28-CRP and SDAI were significantly reduced at 24 and 48 weeks compared with those at baseline. The proportion of CD25 (+) in CD4 (+) T cells in ACPA (+) group was significantly higher than those of ACPA (-) group and HIs at baseline (13.9±5.4% in ACPA (+) group; 6.7±2.9% in ACPA (-) group, p=0.0089; 7.1±4.6% in HIs, p<0.0001). The proportion of CD25 (+) in CD4 (+) T cells decreased at 24 and 48 weeks (13.9±5.4% at baseline; 6.6±5.8% at 24 weeks, p<0.0001; 6.1±3.1% at 48 weeks, p<0.0001). However, ACPA titers were not significantly changed at 24 and 48 weeks compared with those at baseline.

Conclusions 48-week T cell co-stimulation blockade reduces disease activities and the proportion of CD25 (+) in CD4 (+) T cells but not the ACPA titers in ACPA (+) RA patients.

Disclosure of Interest M. Murakami Speakers bureau: Bristol-Myers Squibb Japan, M. Ito: None declared, M. Sekiguchi Grant/research support: Bristol-Myers Squibb Japan, Speakers bureau: Bristol-Myers Squibb Japan, K. Matsui Grant/research support: Bristol-Myers Squibb Japan, M. Kitano Grant/research support: Bristol-Myers Squibb Japan, Y. Imura Grant/research support: Bristol-Myers Squibb Japan, K. Ohmura Grant/research support: Bristol-Myers Squibb Japan, T. Fujii Grant/research support: Bristol-Myers Squibb Japan, T. Kuroiwa: None declared, K. Maeda: None declared, S. Morita: None declared, Y. Kawahito Grant/research support: Bristol-Myers Squibb Japan, T. Mimori Grant/research support: Bristol-Myers Squibb Japan, H. Sano Grant/research support: Bristol-Myers Squibb Japan, N. Nishimoto Grant/research support: Bristol-Myers Squibb Japan

DOI 10.1136/annrheumdis-2014-eular.3997

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