Identification of specific autoantigens in Sjögren's syndrome by SEREX

Abstract

SummaryWe carried out SEREX (serological analysis of antigens by recombinant cDNA expression cloning) using sera from patients with Sjögren's syndrome (SjS) and investigated the frequencies of autoantibodies against autoantigens identified by SEREX in the sera of healthy individuals (HI) and patients with SjS, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). IFI16 and two kelch-like proteins, KLHL12 and KLHL7, were found to be novel autoantigens in SjS by SEREX. A markedly high frequency of anti-IFI16 autoantibodies was observed in the sera of SjS (SjS, 70%; RA, 13%; SLE, 33%; HI, 0%). Interestingly, all serum samples from SjS demonstrated immunoreactivity against one or both of IFI16 and SS-B/La. The presence of autoantibodies against KLHL12 and KLHL7 in the sera was significantly specific to SjS (23% and 17%, respectively), as they were not detected in RA, SLE or HI. Furthermore, we confirmed that transcripts of these autoantigens were expressed preferentially in the salivary glands and immuno-privileged testes. Our results suggest these autoantigens may be useful as serological markers for the clinical diagnosis of SjS and may play a crucial role as organ-specific autoantigens in the aetiopathogenesis of SjS. This study warranted clinical evaluations of autoantibodies against IFI16, KLHL12 and KLHL7 in combination with anti-SS-B/La autoantibodies.

Phenotype Associated With Mutation in the Recently Identified Autosomal Dominant Retinitis Pigmentosa KLHL7 Gene

“…13 No other clinical implications of altered function of KLHL7 have been reported, but antibodies have been detected in patients with Sjögren syndrome. 14 In the present family, Schirmer test revealed no signs of dry eye, which is associated with Sjögren syndrome.…”

The emerging role of human PYHIN proteins in innate immunity: Implications for health and disease

“…IFI16 is a target for autoantibodies and several studies have shown the presence of anti-IFI16 autoantibodies in chronic autoimmune diseases such as SLE [64], systemic sclerosis [65], rheumatoid arthritis [66] and Sjö gren's syndrome [67]. IFI16 is known to relocalise from the nucleus to the cytosol following UV treatment or viral DNA detection.…”

Mislocalization of the interferon inducible protein IFI16 by environmental insults: Implications in autoimmunity

“…Overexpression of IFI16 drives early steps of an inflammatory response through NF-kB mediated secretion of proinflammatory molecules such as ICAM1, E-selectin, IL-8 and MCP-1 [14,15]. Autoantibodies against IFI16 are present in the sera of patients with systemic sclerosis (SSc) [16], systemic lupus erythematosus (SLE) [17,18], rheumatoid arthritis (RA) [19,20] and Sjö gren's Syndrome (SS) [19]. Recently, it has also been discovered as serum circulating protein in the same autoimmune diseases [21].…”