- To characterize mechanisms of T cell-mediated immune response to exocrine glands in Sjögren's syndrome (SS).
- To investigate the humoral immune response against endogenous antigens and viruses in SS patients.
- To determine the role of apoptosis and its regulation in the etiopathogenesis of SS.
- To identify associations between SS and immune response genes.
- To develop rational bases for non-toxic immunotherapies of SS.
- To identify markers useful in the diagnosis and monitoring of disease activity and efficacy of immunotherapies in SS.
Sjögren's syndrome (SS) affects 0.5-1% of the population worldwide (2-3% among >50 years) and is a common cause of chronic discomfort and suffering in females, especially among the aging population. The target organs are the exocrine glands especially in mucous membranes of the eye and the mouth but also in the respiratory, gastro-intestinal and genito-urinary tracts. Current therapy provides only marginal symptomatic relief. However, the chronic destructive process with its attendant mucous surface disability progresses relentlessly in most patients. Consequently, there is an urgent need to clarify the disease process underlying this chronic disorder of the mucous membranes.
In this Concerted Action a co-ordinated set of studies is proposed to investigate etiologic factors and pathogenic mechanisms in human and experimental SS. The present project is designed to promote interaction of experimental and clinical research, through the cooperation of European rheumatologists, cellular and molecular immunologists, and immunopathologists involved in SS research. The proposed characterization of mucosal immune-regulation and pathogenesis in this chronic inflammatory/autoimmune/rheumatic disease will yield direct important clinical insight into disease mechanisms as a basis for therapeutic measures. The conclusion of these studies will shed light on the development of more precise therapies directed toward the elimination of the proliferating cells present in SS patients. The significance of the proposed studies is underlined by the high prevalence of SS as one of the more common but relatively neglected systemic autoimmune diseases.