Anti-TRIM21 autoantibody and inflammasome interaction in pathogenesis of Sjogren’s syndrome (BA3P.200)

Abstract Sjögren’s syndrome is a chronic autoimmune disorder mainly affecting the exocrine glands and is commonly associated with autoantibodies to TRIM21. This study was undertaken to determine the role of TRIM21-reactive antibodies in pathogenesis of Sjögren’s syndrome. NZM mouse strains (2758, 2328, 2410) were immunized with recombinant TRIM21 protein adsorbed on to alum. Mice were monitored for autoantibodies, serum cytokines and pilocarpine induced salivation. Although all NZM mouse strains generated a robust anti-TRIM21 antibody response, salivary gland dysfunction only occurred in the NZM2758 mice. Moreover, alum immunized NZM2758 mice also displayed some loss of glandular function. Serum levels of IL-1α and CXCL1 were upregulated in alum and alum-TRIM21 treated groups of NZM2758 mice. In contrast, levels of IL-2, IL-5, IL-6 and IL-17 were upregulated, only in the alum-TRIM21 treated mice. Antibodies from TRIM21 immunized mice penetrated live cells in vitro, and showed cytoplasmic staining. Passive transfer of sera from TRIM21 immunized mice induced salivary gland dysfunction in recipient mice, only if the recipients were pre primed with alum. Our study shows that in a genetically susceptible mouse strain, anti-TRIM21 antibodies directly affected salivary gland function and this phenomenon was dependent on the activation of inflammasome pathway. Thus, interaction between innate and adaptive immunity is critical for pathogenesis of Sjögren’s syndrome.