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FRI0327 Abatacept Decreases the Activation of not Only CD4+ T Cells but Also CD14+CD16+ Monocytes and CD86+ Memory B Cells in A Correlation with Disease Activity – Single Center Prospective Cohort Study in Biologics-Naive Rheumatoid Arthritis Patients –
  1. J. Kikuchi1,
  2. H. Kameda1,2,
  3. K. Yoshimoto1,
  4. K. Suzuki1,
  5. T. Takeuchi1
  1. 1Division Of Rheumatology, Department Of Internal Medicine, Keio University School of Medicine
  2. 2Division Of Rheumatology, Department Of Internal Medicine, Toho University Ohashi Medical Center, Tokyo, Japan

Abstract

Background Inflammaroty cells and cytokines have crucial roles in pathogenesis of RA.[1] Although abatacept has same efficacy as cytokine inhibitors, its way of efficacy is different and unique because it is not thought to be direct to cytokines.[2,3] It is important to elucidate the effects of abatacept to inflammaroty cells and cytokines.

Objectives To examine the effect of abatacept by the associations of activated subsets of peripheral blood mononuclear cells (PBMCs), cytokines and clinical and structural data in RA patients in clinical prospective cohort.

Methods Fifty-one biologics-naïve RA patients were prospectively evaluated. Multiple subsets of PBMCs with their activation markers and 9 serum cytokines including interleukin (IL)-6 and tumor necrosis factor (TNF) α were sequentially measured by flowcytometry and high sensitivity electrochemiluminescense assay. Relationships between activated subsets of PBMCs, serum cytokines, the disease activity and radiographic progression were evaluated.

Results Mean disease activity score (DAS) 28-ESR decreased from 5.33 at baseline to 3.43 at week 24. The numbers of HLA-DR+CD4, OX40+CD4, HLA-DR+Th1, HLA-DR+Th2, HLA-DR+Th17, regulatory T cells (Treg) and HLA-DR+Treg significantly decreased at week 24. The ratio of CD69 expression on monocytes also decreased. Changes of HLA-DR expression on Th1, Treg, CD14+CD16+ monocytes and CD86 expression on memory B cells were statistically correlated with those of disease activity (ρ =0.29, p=0.048, ρ =0.35, p=0.016, ρ =0.35, p=0.016 and ρ =0.30, p=0.041, respectively). Change of CD86 expression on memory B cells was correlated with those of CRP, ESR, MMP-3, RF and change of the number of CD86+ B cells was correlated with that of serum IL-6 level (ρ =0.31, p=0.037). Also at the baseline, the expression correlated with serum IL-6 (ρ =0.39, p=0.007). IL-6 levels significantly decreased in patients with EULAR good response (p=0.016). Radiographic progression at week 24 significantly correlated with the baseline serum IL-6 (ρ =0.30, p=0.038) and changes of HLA-DR expression on CD14+CD16+ monocytes and CD161 expression on CD56brightCD16- NK cells (ρ =0.29, p=0.057 and ρ = -0.38, p=0.012).

Conclusions The chronological analysis of peripheral blood in RA patients suggests abatacept inhibits activation of not only CD4+ T cells including Treg but also CD86+ memory B cells and CD14+CD16+ monocytes. In addition, CD56brightCD16- NK cells and serum IL-6 were associated with radiographic progression.

References

  1. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. The New England journal of medicine 2011;365(23):2205-19.

  2. Bathon J, Robles M, Ximenes AC, et al. Sustained disease remission and inhibition of radiographic progression in methotrexate-naive patients with rheumatoid arthritis and poor prognostic factors treated with abatacept: 2-year outcomes. Annals of the rheumatic diseases 2011;70(11):1949-56.

  3. Weinblatt ME, Schiff M, Valente R, et al. Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: findings of a phase IIIb, multinational, prospective, randomized study. Arthritis and rheumatism 2013;65(1):28-38.

Disclosure of Interest J. Kikuchi Consultant for: Pfizer Japan Inc., H. Kameda: None declared, K. Yoshimoto: None declared, K. Suzuki: None declared, T. Takeuchi Grant/research support: Abott Japan Co., LTD., Astellas Pharma, Bristol- Myers K.K., Chugai Pharmaceutical Co., LTD., Daiichi Sankyo Co., LTD., Eisai Co., LTD., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Nippon Shinyaku Co., LTD., Otsuka Pharmaceutical, Pfizer Japan Inc., Sanofi- aventis K.K., Santen Pharmaceutical, Takeda Pharmaceutical Co., LTD., Teijin Phrma Ltd., Consultant for: Astra Zeneca, K.K., Eli-Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Asahi Kasei Medical K.K., Speakers bureau: Abott Japan Co., LTD., Bristol-Myers K.K., Chugai Pharmaceutical Co., LTD., Eisai Co., LTD., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Takeda Pharmaceutical Co., LTD.

DOI 10.1136/annrheumdis-2014-eular.1255

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