Autoimmune response and target autoantigens in Sjogren’s syndrome
John G. Routsias,
Athanasios G. Tzioufas,
John G. Routsias
Department of Pathophysiology, School of Medicine, University of Athens, Greece
Search for more papers by this authorAthanasios G. Tzioufas
Department of Pathophysiology, School of Medicine, University of Athens, Greece
Search for more papers by this authorJohn G. Routsias,
Athanasios G. Tzioufas,
John G. Routsias
Department of Pathophysiology, School of Medicine, University of Athens, Greece
Search for more papers by this authorAthanasios G. Tzioufas
Department of Pathophysiology, School of Medicine, University of Athens, Greece
Search for more papers by this authorAthanasios G. Tzioufas MD, Department of Pathophysiology, School of Medicine, University of Athens, 75 M Asias St, 11527 Athens Greece. Tel.: +30 210 746 2670; fax: +30 210 746 2664; e-mail: [email protected]
Abstract
Eur J Clin Invest 2010; 40 (11): 1026–1036
Background Primary Sjogren’s syndrome (pSS) is characterized by the presence of autoantibodies targeting mainly the Ro/La ribonucleoprotein complex. It is now appreciated that the production of autoantibodies is an antigen-driven immune response.
Design In this review, candidate mechanisms for autoantigen presentation and perpetuation of the autoimmune response within the autoimmune tissue lesion of pSS are discussed.
Results Several studies have shown that the epithelial cell in labial salivary glands of patients with Sjogren’s syndrome is activated, bearing characteristics of an antigen-presenting cell, as suggested by inappropriate expression of class II HLA and co-stimulatory molecules. Other studies have confirmed that in salivary glands, there is an increased autoantigen presentation via apoptotic blebs and bodies, exosomes and heat shock protein-mediated cross-priming. There is also an increased expression of interferon (IFN)-induced genes, such as the autoantigen Ro52, which provide negative feedback regulation in inflammation. Ro60 and La autoantigens also appear to play a major role in the local autoimmune response in Sjogren’s syndrome. In this regard, La and Ro60 the messenger RNA (mRNA) expression is upregulated in the affected salivary glands with different isoforms of La autoantigen mRNA to be expressed in patients with pSS. At the protein level, La/SSB in pSS salivary glands is found to be post-translationally modified.
Conclusions Autoantigen alterations in a microenvironment of local inflammation with increased in situ apoptosis, Toll-like receptor (TLR) signalling and antigen presentation may drive the autoimmune response and local autoantibody production in pSS.
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