Novel NLRP3/cryopyrin mutations and pro-inflammatory cytokine profiles in behçet's syndrome patients

Abstract

Behçet's syndrome (BS) is a systemic inflammatory disorder with unknown etiology. Features of both innate and adaptive immunity have been claimed in the pathogenesis of BS. To test the possible dysregulation of the NLRP3/cryopyrin (Nod-like receptor with a pyrindomain 3) inflammasome, as a result of mutation(s), we performed single-strand conformation polymorphism analyses and/ or sequencing of all the coding regions and intron-exon boundaries of NLRP3/cryopyrin and ASC (apoptosis-associated speck-like protein containing CARD) genes from Turkish BS patients and healthy controls. At the same time, we determine pro-inflammatory cytokine secretion profiles of peripheral blood cells in response to LPStreatment using ELISA. BS patients with vascular involvement showed significantly increased levels of TNF-α release at 2-, 4- and 8-h post-treatment and significantly increasedIL-1β levels were detected at 2 h (P = 0.005) and 4 h (P = 0.025) (n = 10). We identified four mutations in the NLRP3/cryopyrin gene, V200M (n = 3/104) and T195M (n = 1/104), inBS patients but none in control samples. No mutations were detected in the ASC gene. The effect of these NLRP3/cryopyrin mutants on ASC speck assembly and IL-1β secretion was testedand the V200M mutant was shown to induce IL-1β secretion. Thus, it is likely that certainmutations in NLRP3/cryopyrin in combination with yet unknown other factors may contribute to the proinflammatory cytokine profiles in BS patients. © The Japanese Society for Immunology. 2013. All rights reserved.