Enhanced expression of NLRP3 inflammasome-related inflammation in peripheral blood mononuclear cells in Sjögren's syndrome

Abstract

Objective: The aim of this study was to identify the association of NLRP3 inflammasome-induced inflammation with disease activity and damage in Sjögren's syndrome.

Methods: A total of 33 female patients with Sjögren's syndrome and 34 sex- and age-matched, healthy controls were consecutively enrolled. The mRNA expression levels of NLRP3, ASC, caspase-1, interleukin-1β (IL-1β), and IL-18 in peripheral blood mononuclear cells (PBMCs) were measured, as well as serum IL-1β and IL-18 protein expression levels. Protein levels for mature IL-1β (p17) and caspase-1 (p20) were analyzed by western blotting. The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) and Sjögren's Syndrome Disease Damage Index (SSDDI) were also evaluated.

Results: Patients with Sjögren's syndrome group showed higher expression of mRNA IL-1β and IL-1β at the protein level than controls (p<0.001 of both). Enhanced expression of mature IL-1β (p17) and caspase-1 (p20) proteins in Sjögren's syndrome were noted, compared to controls. The mRNA levels of caspase-1 and ASC were significantly increased in patients with Sjögren's syndrome compared to controls (p=0.001 and p=0.002, respectively). Based on the SSDDI scores, patients with damage (SSDDI≥1) had higher IL-1β mRNA expression compared to patients without damage (SSDDI=0) (p=0.034). SSDDI scores were closely related with IL-18 protein levels (r=0.357, p=0.041). The levels of IL-1β mRNA and IL-1β protein were correlated with the mRNA level of NLRP3 (r=0.597, p<0.001 and r=0.502, p=0.003, respectively). IL-1β mRNA expression was responsible for the presence of damage for Sjögren's syndrome (p=0.034).

Conclusion: This study confirmed that NLRP3 inflammasome-mediated inflammation might be implicated in the pathogenesis of Sjögren's syndrome.

Keywords: Inflammasome; Interleukin-18; Interleukin-1β; NLRP3; Sjögren's syndrome.