abstract details

The summaries are free for public use. ARTHROS will continue to add and archive summaries of articles deemed relevant to ARTHROS by our Faculty.

The initiation of autoimmunity at epithelial surfaces: a focus on rheumatoid arthritis and systemic lupus erythematosus

Author information

Pentony P1, Duquenne L1, Dutton K1, Mankia K1, Gul H1, Vital E1, Emery P1. Discov Med. 2017 Nov;24(133):191-200.

Abstract

Author information

1 Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, LS7 4SA, U.K.

Abstract

It is well established that the autoantibodies that characterize both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are present systemically years before patients develop disease. In both these autoimmune rheumatic diseases, evidence is growing that local autoimmune processes occur at epithelial surfaces potentially initiating localized autoimmunity. For RA, these are mucosal surfaces including the oral mucosa, lung, and gut. At the oral mucosa and lung, risk factors such as periodontal disease and smoking may contribute to autoimmunity by driving the local generation of citrullinated autoantigens. For SLE, the skin may be integral in pathogenesis. It is proposed that defective clearance of apoptotic debris leads to initial innate immune responses preceding autoimmunity. Many tissues may be implicated but the frequency of skin disease, even without autoantibodies, and the role of UV light as a trigger suggest that keratinocytes may be a key site of initiation. In both diseases, a local break in immune tolerance could lead to systemic autoimmunity, and, in the gut, bacterial organisms that colonize the intestine may influence the localized gut immune response through T-cells and promote the development of systemic autoimmunity. In this review, we discuss the evidence for localized epithelial autoimmunity in those at risk of RA and SLE and early disease. Localized autoimmunity at the oral mucosa, lung, gut, and skin will be considered as potential initiating sites of ARD-related autoimmunity.