Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose: Inflammasomes are intracellular multiprotein complexes that sense pathogenic microorganisms, as well as danger signals released following tissue injury. Such activation of inflammasome leads to the upregulation of various inflammasome-related molecules and the release of pro-inflammatory cytokines, namely interleukin-1β (IL-1β) and interleukin-18 (IL-18). In this study, we sought to investigate the inflammasome activation status in the peripheral blood and the salivary gland (SG) tissues of SS patients and its relationship with indices of disease activity and severity.
Methods: PBMC mRNA expression of inflammasome-related molecules NLRP3, AIM2, ASC, pro-caspase-1, IL-1β, IL-18 as well as the interferon type I signature genes MX1 and IF44L was evaluated by RT-PCR. Serum expression of inflammasome proteins ASC, IL-1β and IL-18 was evaluated by ELISA. SG biopsies were examined for the presence of inflammasome-related proteins by confocal microscopy.
Results: Compared to healthy controls (n=20), SS patients exhibited significantly higher serum levels of ASC (n=56; p=0.002), IL-1β (n=37; p=0.003) and IL-18 (n=33; p<0.0001). The serum levels of ASC protein were significantly higher in SS patients at high risk for lymphoma development (SS-type I; n=17) and in SS patients with lymphoma (n=28), compared to SS patients with low risk for lymphoma development (SS-type II; n=11, for p=0.030 and p=0.004, respectively). In SS patients, the serum levels of ASC and IL-18 correlated positively with the total cumulative ESSDAI score values (p=0.005 and p=0.006, respectively), whereas ASC levels correlated with the presence of C4 hypocomplementemia (p=0.002), rheumatoid factor (p=0.02) and purpura (p=0.02). In addition, compared to healthy controls (n=16), the PBMC of SS patients expressed significantly higher levels of ASC, NLRP3, IL-1β, IL-18 and pro-caspase-1 transcripts (n=39, p<0.05). The calculation of the NLRP3-inflammasome score in PBMC indicated an optimal discrimination between SS clinical subgroups (AUC=0.915) and positively correlated with interferon type I expression (Spearman r=0.443, p= 0.0006, n=37). In the SG tissues of SS patients, CD68+ macrophages and epithelial cells manifested high expression of ASC protein that was localized in perinuclear aggregates (specks), suggesting inflammasome activation. Co-localization experiments showed significantly increased ASC expression in CD68+ macrophages in SS (p<0.0001), compared with non-SS control patients.
Conclusion: Our findings indicate that SS patients manifest evidence of inflammasome activation in both peripheral blood and the SG tissues. Several indices of inflammasome activation correlated with the presence of severe disease, as well as lymphoma development and may constitute valuable clinical biomarkers for these patients.
To cite this abstract in AMA style:Vakrakou AG, Boiu S, Manoussakis MN. Evidence of Inflammasome Activation in the Peripheral Blood and Salivary Gland Tissues of Primary Sjögren’s Syndrome Patients: Correlation with Clinical Indices of Severe Disease and Lymphoma Development [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/evidence-of-inflammasome-activation-in-the-peripheral-blood-and-salivary-gland-tissues-of-primary-sjogrens-syndrome-patients-correlation-with-clinical-indices-of-severe-disease-and-lymphoma/. Accessed December 2, 2020.
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