Background In an open-label proof of concept study, Abatacept has been identified as an effective and safe treatment modality in primary Sjögren's syndrome (pSS).1 Abatacept is a fully human fusion molecule of IgG-Fc and CTLA-4 that modulates the costimulatory interaction between APCs and T-lymphocytes, thereby inhibiting full T-cell activation and T-cell dependent activation of B-cells. Modifying T-helper (Th-) cell homeostasis may contribute to the therapeutic effect of Abatacept as Th-cell subset imbalances are involved in the emergence of autoimmune diseases.
Objectives To assess Th-cell homeostasis in peripheral blood of pSS patients in response to Abatacept treatment.
Methods Fifteen patients with pSS, diagnosed according to the revised AECG criteria, were treated with Abatacept on days 1, 15, 29 and every 4 weeks thereafter for 5 months ($≈ $10 mg/kg of body weight i.v.). Absolute numbers and frequencies of circulating Th-cell subsets (CD3+CD4+) were examined in fresh blood samples by 6-color flow cytometry at baseline and 4, 12, 16, 24, 36 and 48 weeks after the first dose. Expression patterns of chemokine receptors CCR7 and CD45RO were used for distinction between naive (CCR7+CD45RO–), central memory (CCR7+CD45RO+), effector memory (CCR7–CD45RO+) and terminally differentiated (CCR7–CD45RO–) Th-cells. At the time of these analyses, few samples were not examined yet. Generalized estimating equations (GEE) were used to analyze the presence of different subsets over time within subjects, viz. on treatment (week 0-24) and off treatment (week 24-48).
Results On treatment, numbers of peripheral blood CD4+ T-cells did not significantly differ from baseline values. However, absolute numbers and frequencies of total memory Th-cells decreased during treatment. This was a result of a decrease in effector memory Th-cells, but not central memory Th-cells. On treatment, both absolute numbers and frequencies of effector memory Th-cells decreased significantly over time (p<0.001), with the largest decrease seen at week 24 (Fig. 1). On the contrary, absolute numbers and frequencies of naive Th-cells increased over time (p=0.12 and p<0.001, resp.). From week 24 to week 48 (off treatment), a trend towards increased absolute numbers and frequencies of effector memory Th-cells was observed over time (p=0.031 and p=0.14, resp.). Decrease and repopulation of this T-cell subset are in line with changes in disease activity as assessed with ESSDAI.1
Conclusions Abatacept treatment decreases the presence of effector memory Th-cells in peripheral blood of pSS patients. The observation that decrease and recovery of effector memory Th-cells correspond to changes in disease activity suggests that these cells are -at least partially- responsible for the effects of Abatacept seen in pSS patients. A future study will focus on the extent to which different types of effector cells are affected by Abatacept.
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.
Acknowledgements Supported by an unrestricted grant and study medication by BMS, France.
Disclosure of Interest None declared