Abstract
ABATACEPT TREATMENT SUPPRESSES T CELL ACTIVATION IN ANTI-CYCLIC CITRULLINATED PEPTIDE ANTIBODY (ACPA) POSITIVE RA PATIENTS BUT NOT IN ACPA NEGATIVE RA PATIENTS
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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 JapanCitation: , volume 72, supplement s3, year 2013, page Session: Poster Tour: Update on non-TNF inhibitors in RA
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17 organizations
Organization
Osaka Rheumatology Clinic, OsakaOrganization
Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya cityOrganization
Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, KyotoOrganization
Department of Hematology and Rheumatology, Kinki University School of Medicine, Osakasayama cityOrganization
Yokota Clinic for Rheumatology, Osaka