Abstract
Inflammasome activation in the innate immune response plays a role in the pathogenesis of psoriasis largely due to the increased levels of pro-inflammatory cytokines. However, the precise role of inflammasomes in psoriasis (Ps) and psoriatic arthritis (PsA) is largely undefined. To establish the reliability of inflammasome signaling proteins as diagnostics and predictive biomarkers of clinical severity in this disease population, serum from healthy donors and patients with Ps/PsA were analyzed for the protein expression of caspase-1, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), interleukin (IL)-1β and IL-18 levels to determine cut-off points, positive and negative predictive values, and receiver operator characteristic (ROC) curves. Our data revealed that ASC and IL-18 proteins were significantly higher in the Ps group when compared to healthy controls. The area under the curve (AUC) for ASC was 0.9224 with a cut-off point of 321.8 pg/ml, while IL-18 had an AUC of 0.7818 and a cut-off point of 232.1 pg/ml. In addition, levels of IL-18 had a statistically significant linear correlation with that of ASC with an adjusted R squared of 0.2566, indicating that approximately 25% of IL-18 levels could be explained by ASC levels in serum. Our findings indicate that ASC and IL-18 play a significant role in the inflammatory response associated with the pathology of Ps. These inflammasome proteins appear to be key biomarkers in determining diagnoses in this patient population.
Highlights
Psoriasis (Ps) is a chronic immune-mediated systemic disease that affects over 125 million people globally and has damaging effects that extend well beyond the dermis
These findings suggest that Ps pathogenesis involves the activation of the inflammasome multiprotein complex, which is involved in the production of interleukin (IL)-1b and IL-18, two inflammatory cytokines seen in Ps pathogenesis
These findings indicate that a caspase-recruitment domain (ASC) and IL-18 play a significant role in the inflammatory response in the pathology of Ps
Summary
Psoriasis (Ps) is a chronic immune-mediated systemic disease that affects over 125 million people globally and has damaging effects that extend well beyond the dermis. We evaluated the potential for inflammasome signaling proteins to serve as biomarkers that could be used in the clinical setting to determine the diagnosis of Ps. Serum samples from healthy donors were analyzed for protein expression levels of caspase-1, ASC, IL-1b, and IL-18 and were compared to serum levels in patients with Ps. Cut-off points, positive and negative predictive values, and receiver operator characteristic (ROC) curves with associated sensitivity and specificity calculations were determined for each of these inflammasome proteins. A binomial logistic regression analyses of the probability of a patient having Ps/PsA (separated into biologic-treated, nonbiologic treated group, and untreated) as determined by the levels of ASC and IL-18 were run using RStudio/RMarkdown software. Models were evaluated by comparing the Akaike information criterion (AIC) value among the different tested models
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