Introduction:

Uric Acid (UA) is a marker of disease risk and severity in SScPAH. UA is a recognised activator of the NLRP3 inflammasome, which is composed of apoptosis-associated speck-like protein containing CARD (ASC), caspase-1, & NOD-like receptor protein 3 (NLRP3); it causes production of bioactive proinflammatory cytokines interleukin(IL)-1? and IL-18.

Aims and Objectives:

We hypothesized that NLRP3 inflammasome activation plays a role in the pathogenesis of SSc-PAH. We aimed to evaluate components of the NLRP3 inflammasome pathway in SSc-PAH circulation versus controls.

Methods:

Serum samples were obtained from peripheral vein (PV), right ventricle (RV) and pulmonary artery (PA) during right heart catheterisation in patients with SSc-PAH (n=16), SSc-nonPAH (n=18), Chronic Thrombo-Embolic PH (n=13) and healthy controls (n=10). Levels of UA, P2X7, NLRP3, ASC, IL-18 and IL-1? were measured using ELISA (pg/mL).

Results:

In PV and RV, IL-1? was higher in SSc-PAH vs. healthy controls (22 vs. 0, p=0.04 and 20 vs. 0, p=0.047). In PV, IL-18 was higher in SSc-PAH vs. healthy controls (364 vs. 193, p=0.027) and vs. SSc-nonPAH (258, p=0.2). Neither IL-1? nor IL-18 were significantly higher in CTEPH than healthy controls (p=0.56 & p=0.12). In SSc-PAH, in PV, UA, NLRP3 and ASC correlated positively with mPAP (p=0.003, 0.039 & 0.047) and in the PA, ASC and NLRP3 correlated with IL-18 (p=0.001 & p=0.017).

Conclusions:

Our findings demonstrate an association between components, upstream activators and downstream cytokines of the NLRP3 inflammsome in SSc-PAH, suggesting local activity of this inflammatory pathway within the pulmonary vasculature in SSc-PAH.