ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 3205

Treatment with Abatacept or Rituximab Targets T Follicular Helper Cells in Patients with Primary Sjogren s Syndrome

Gwenny M. Verstappen1, Petra M. Meiners2, Odilia B.J. Corneth3, Rudi W. Hendriks3, Arjan Vissink4, Frans G.M. Kroese5 and Hendrika Bootsma5, 1Rheumatology & Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands, 2Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Groningen, Netherlands, 3Pulmonary Medicine, Erasmus MC, Rotterdam, Netherlands, 4Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Groningen, Netherlands, 5Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: , ,

Session Information

Date: Tuesday, November 10, 2015

Title: Sjögren's Syndrome II: Clinical Discoveries

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: T cell-dependent B cell hyperactivity is a characteristic pathogenetic feature of primary Sjögren’s syndrome (pSS). This is illustrated by the finding that treatment of pSS patients with either abatacept or rituximab improves disease activity [1-2]. However, the mode of action of both treatment modalities in pSS remains elusive. The current study assessed the impact of abatacept or rituximab treatment on circulating CD4+memory T cell subsets in pSS patients. 

Methods: Fifteen pSS patients treated with abatacept and twenty-four pSS patients treated with rituximab were included in this study [1-2]. Percentages of CD4+memory T cell subsets were assessed by flow cytometry analysis of peripheral blood mononuclear cells from patients at baseline, during treatment and after treatment. 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, T follicular helper (Tfh) and T regulatory (Treg) subsets. 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: Treatment with abatacept or rituximab results in a decrease in absolute numbers of Tfh cells (CXCR5+PD-1+) (p<0.001 for both treatments). Furthermore, expression levels of the activation marker ICOS by Tfh cells became concomitantly lower (p<0.001 for both treatments). Absolute numbers of Treg cells (FoxP3+) were only reduced by abatacept (p<0.001). In contrast, other CD4+memory T cell subsets (Th1, Th2, Th17 cells) were unaffected. Off treatment (week 24-48), changes in Tfh cells, ICOS expression and Treg cells reversed to baseline levels.

Conclusion: Treatment of pSS patients with abatacept or rituximab primarily affects Tfh cells. The lower numbers of Tfh cells may lead to reduced T cell-dependent B cell hyperactivity and contribute to the beneficial clinical effects of both treatment modalities in pSS patients. These findings indicate that Tfh cells may play a central role in the pathogenesis of pSS.

  1. Meiners PM, et al. Abatacept treatment reduces disease activity in early primary Sjogren’s syndrome (open-label proof of concept ASAP study). Ann Rheum Dis 2014;73:1393-6
  2. Meiners PM, et al. Responsiveness of disease activity indices ESSPRI and ESSDAI in patients with primary Sjögren’s syndrome treated with rituximab. Ann Rheum Dis 2012;71:1297-302
Disclosure: G. M. Verstappen, None; P. M. Meiners, None; O. B. J. Corneth, None; R. W. Hendriks, None; A. Vissink, None; F. G. M. Kroese, None; H. Bootsma, Roche Pharmaceuticals, 2,Bristol-Myers Squibb, 2.

To cite this abstract in AMA style:

Verstappen GM, Meiners PM, Corneth OBJ, Hendriks RW, Vissink A, Kroese FGM, Bootsma H. Treatment with Abatacept or Rituximab Targets T Follicular Helper Cells in Patients with Primary Sjogren s Syndrome [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/treatment-with-abatacept-or-rituximab-targets-t-follicular-helper-cells-in-patients-with-primary-sjogren-s-syndrome/. Accessed .

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