Inhibitors of T cell Activation in the Treatment of Sjögren’s Syndrome

Abstract

Given the hypothesis of an initial exogenous agent attacking/infecting ocular and oral glands in Sjögren’s syndrome, we propose a primarily T cell-guided reaction with ensuing recruitment of B cells and finally resulting in auto-antibody production. From an immunological standpoint, the first clinical signs do represent established disease. Nevertheless, targeted therapy should start as early as possible, and they may target B as well as T cells. A primarily local therapy by CsA eye-drops is worthwhile applying in case of strictly ocular involvement only. Otherwise, a short cycle of leflunomide might prove efficient. If not, based on the most possibly underlying pathophysiology of T and B cell interaction and our own experience, a 6-month treatment with abatacept during the early phase of disease can reach the target cells and lead to clinical improvement. In the later stages, especially in case of cryoglobulinemic vasculitis or pulmonary involvement, a B cell depletional therapy may be highly effective. Based on the available data, it would be interesting to initiate a study targeting both cellular arms of the adaptive immune system, i.e., B cell depletion with, e.g., rituximab and T cell inhibition using abatacept. Trials with alefacept have shown T cell-targeted, positive effects on exocrine gland function in a primary SS (pSS)-associated non-obese diabetic (NOD) mouse model. Whether this molecular intervention is beneficial in human disease will have to be shown.