Background T-cell dependent B-cell hyperactivity is a characteristic feature of primary Sjögren's syndrome (pSS). Abatacept, a human fusion molecule of IgG-Fc and CTLA-4, inhibits the costimulatory interaction between antigen-presenting cells and T-cells, thereby inhibiting full T-cell activation and T-cell dependent B-cell activation. Treatment of early and active pSS patients with abatacept improves disease activity [1,2]. However, the mode of action of abatacept in pSS remains elusive.
Objectives The current study was designed to assess the impact of abatacept treatment on effector T-cell subsets in pSS patients.
Methods Fifteen pSS patients, diagnosed according to the 2002 AECG criteria , were treated with abatacept for 24 weeks . Percentages of effector CD4+ T-cell subsets were assessed in peripheral blood mononuclear cells by flow cytometry at baseline, and 4, 12, 24, 36 and 48 weeks after the first dose. Expression patterns of CD45RA, CXCR3, CCR6, CCR4, CXCR5, programmed death-1 (PD-1), inducible costimulator (ICOS) and FoxP3 were used for distinction of Th1, Th2, Th17, Tfh and Treg subsets. Serum levels of effector T-cell related cytokines were measured at all time points using Luminex. Generalized estimating equations were used to analyze the presence of different subsets over time within patients, viz. on treatment (week 0-24) and off treatment (week 24-48).
Results Percentages of Tfh-cells (CXCR5+PD-1+ within total CD4+ T-cells) decreased on abatacept treatment (week 0-24; p=0.001). Furthermore, expression levels of ICOS by Tfh-cells became concomitantly lower (p<0.001). Treg-cells (FoxP3+ within total CD4+ T-cells) were also reduced on treatment (p<0.001), whereas levels of Th1, Th2 and Th17-cells were unaffected. Analysis of effector T-cell related cytokines in serum revealed that IL-21 concentrations decreased on treatment (p<0.001). All these changes reversed off treatment (week 24-48).
Conclusions Treatment of pSS patients with abatacept primarily affects Tfh-cells. The lower numbers of Tfh-cells may lead to reduced T-cell-dependent B-cell hyperactivity and contribute to the clinical effects of abatacept treatment in pSS patients.
Meiners et al., Abatacept treatment reduces disease activity in early primary Sjögren's syndrome (open-label proof of concept ASAP study). Ann. Rheum. Dis Published Online First: 28 Jan 2014.
Adler et al., Evaluation of Histologic, Serologic, and Clinical Changes in Response to Abatacept Treatment of Primary Sjögren's Syndrome: A Pilot Study. Arthritis Care Res (Hoboken) 2013;65:1862–8.
Vitali et al., Classification criteria for Sjögren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann. Rheum. Dis 2002;61:554-8.
Acknowledgements Supported by an unrestricted grant and study medication by Bristol-Myers Squibb, France.
Disclosure of Interest None declared