The aim of this study was to identify the association of NLRP3 inflammasome-induced inflammation with disease activity and damage in Sjögren's syndrome.
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.
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).
This study confirmed that NLRP3 inflammasome-mediated inflammation might be implicated in the pathogenesis of Sjögren's syndrome.