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SAT0101 Abatacept Treatment Suppresses T Cell Activation in Anti-Cyclic Citrullinated Peptide Antibody (ACPA) Positive RA Patients but not in Acpa Negative RA Patients
  1. T. Matsutani1,
  2. M. Murakami1,2,
  3. M. Sekiguchi3,
  4. K. Matsui3,
  5. M. Kitano3,
  6. M. Namiki3,
  7. K. Ohmura4,
  8. Y. Imura4,
  9. T. Fujii4,
  10. T. Kuroiwa5,
  11. H. Nakahara6,
  12. S. Hika6,
  13. K. Maeda6,
  14. Y. Nozaki7,
  15. M. Funauchi7,
  16. K. Murakami8,
  17. T. Ikawa9,
  18. S. Irimajiri10,
  19. A. Nampei11,
  20. T. Azuma12,
  21. T. Sasaki13,
  22. A. Yokota14,
  23. S. Morita15,
  24. Y. Kawahito16,
  25. T. Mimori4,
  26. H. Sano3,
  27. N. Nishimoto1,2,17
  1. 1Laboratory of Immune Regulation, Wakayama Medical University
  2. 2Osaka Rheumatology Clinic, Osaka
  3. 3Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya city
  4. 4Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto
  5. 5Department of Rheumatology, Yukioka Hospital
  6. 6Division of Allergy, Rheumatology and Connective Tissue Diseases, Department of Internal Medicine, NTT West Osaka Hospital, Osaka
  7. 7Department of Hematology and Rheumatology, Kinki University School of Medicine, Osakasayama city
  8. 8Department of Rheumatology, Osaka Red Cross Hospital, Osaka
  9. 9Department of Rheumatology, Kobe Konan Yamate Clinic, Kobe
  10. 10Department of Rheumatology, Rinku General Medical Center, Izumisano
  11. 11Department of Orthopaedic Surgery, Osaka Rosai Hospital, Sakai
  12. 12Department of internal medicine, Tenri Yorozu Sodansyo Hospital, Tenri city
  13. 13Department of Orthopaedic Surgery, Nishinomiya Watanabe Hospital, Nishinomiya city
  14. 14Yokota Clinic for Rheumatology, Osaka
  15. 15Department of Biostatistics and Epidemiology, Graduate School of Medicine & Medical Center, Yokohama City University, Yokohama
  16. 16Department of Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto
  17. 17Institute of Medical Science, Tokyo Medical University, Tokyo, Japan

Abstract

Background We have reported that abatacept (ABA) treatment suppressed T cell activation and reduced plasma levels of interleukin (IL)-6 in rheumatoid arthritis (RA) patients. Anti-cyclic citrullinated peptide antibodies (ACPA) are highly specific and sensitive marker for RA. Production of autoantibody such as ACPA depends largely on an interaction between CD4+ helper T cells and antibody-producing B cells.

Objectives The aim of this study is to elucidate different effect of ABA on T cell activation, T cell subsets and cytokine profiles between ACPA+ an ACPA− patients with RA.

Methods PBMCs and plasmas were collected from healthy individuals (n=15) and RA patients (n=45) enrolled in abatacept research outcome as a first-line biological agent in the real world (ABROAD study) at baseline and 24 weeks after ABA treatment. Surface phenotypes and activation markers of T cells were analyzed with FACS. Treg cells (CD4+CD25+Foxp3+) were measured with intracellular staining with anti-Foxp3 antibody. After in vitro stimulation with PMA/Ionomycin, cells were intracellularly stained with anti-IFN-γ, anti-IL-4 or anti-IL-17A antibodies. ACPA titers were determined with EliA™ CCP ELISA kit.

Results At baseline, there were no significant differences in CRP, DAS28-CRP, MMP-3 between ACPA+ (>4.5U/mL, n=38) and ACPA− RA patients (n=7). Remission rate (DAS28-CRP<2.3) at 24 weeks was 43% (16/38) in ACPA+ and 14% (1/7) in ACPA− patients, respectively. Changes of DAS28-CRP during 24 weeks of ABA treatment were greater in ACPA+ (2.0±1.1) than in ACPA− patients (1.3±0.66). Proportion of CD25+ in CD4+ T cells was higher in ACPA+ than in ACPA− patients at baseline and significantly decreased in ACPA+ (11.1±5.6% → 5.5±5.0%, P<0.001) but not in ACPA− patients (5.9±2.9% → 4.4±3.0%) after ABA treatment. The proportions of Treg, Th2 and Th17 cells significantly decreased in only ACPA+ patients.

Conclusions CD4+ T cells were more activated in ACPA+ patients who responded well to ABA treatment than in ACPA− patients. ABA treatment reduced activated CD4+CD25+ T cells in ACPA+ patients but not in ACPA− patients. It is suggested that ABA has more effective on ACPA+ patients by suppressing T cell activation.

Disclosure of Interest T. Matsutani Speakers bureau: Bristol-Myers Squibb Japan, M. Murakami: None Declared, M. Sekiguchi Grant/research support from: Bristol-Myers Squibb Japan, Speakers bureau: Bristol-Myers Squibb Japan, K. Matsui Grant/research support from: Bristol-Myers Squibb Japan, M. Kitano Grant/research support from: Bristol-Myers Squibb Japan, M. Namiki Grant/research support from: Bristol-Myers Squibb Japan, K. Ohmura Grant/research support from: Bristol-Myers Squibb Japan, Y. Imura Grant/research support from: Bristol-Myers Squibb Japan, T. Fujii Grant/research support from: Bristol-Myers Squibb Japan, T. Kuroiwa: None Declared, H. Nakahara: None Declared, S. Hika: None Declared, K. Maeda: None Declared, Y. Nozaki Grant/research support from: Bristol-Myers Squibb Japan, M. Funauchi Grant/research support from: Bristol-Myers Squibb Japan, K. Murakami: None Declared, T. Ikawa: None Declared, S. Irimajiri: None Declared, A. Nampei: None Declared, T. Azuma: None Declared, T. Sasaki: None Declared, A. Yokota: None Declared, S. Morita: None Declared, Y. Kawahito Grant/research support from: Bristol-Myers Squibb Japan, T. Mimori Grant/research support from: Bristol-Myers Squibb Japan, H. Sano Grant/research support from: Bristol-Myers Squibb Japan, N. Nishimoto Grant/research support from: Bristol-Myers Squibb Japan

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