Forouzandeh Mahtab, Besen Jaren, Keane Robert W, de Rivero Vaccari Juan Pablo
The Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, United States.
Department of Neurological Surgery and The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, United States.
Front Pharmacol. 2020 Aug 11;11:1238. doi: 10.3389/fphar.2020.01238. eCollection 2020.
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.
先天性免疫反应中的炎性小体激活在银屑病发病机制中起作用,这主要归因于促炎细胞因子水平的升高。然而,炎性小体在银屑病(Ps)和银屑病关节炎(PsA)中的确切作用在很大程度上尚不清楚。为了确定炎性小体信号蛋白作为该疾病人群临床严重程度的诊断和预测生物标志物的可靠性,分析了健康供体以及Ps/PsA患者血清中半胱天冬酶-1、含半胱天冬酶招募结构域的凋亡相关斑点样蛋白(ASC)、白细胞介素(IL)-1β和IL-18的蛋白表达水平,以确定临界值、阳性和阴性预测值以及受试者工作特征(ROC)曲线。我们的数据显示,与健康对照相比,Ps组中ASC和IL-18蛋白显著更高。ASC的曲线下面积(AUC)为0.9224,临界值为321.8 pg/ml,而IL-18的AUC为0.7818,临界值为232.1 pg/ml。此外,IL-18水平与ASC水平具有统计学意义的线性相关性,调整后的决定系数R平方为0.2566,这表明血清中IL-18水平的约25%可由ASC水平解释。我们的数据表明,ASC和IL-18在与Ps病理相关的炎症反应中起重要作用。这些炎性小体蛋白似乎是确定该患者群体诊断的关键生物标志物。