Rieber Nikolaus, Gavrilov Alina, Hofer Laura, Singh Anurag, Öz Hasan, Endres Theresa, Schäfer Iris, Handgretinger Rupert, Hartl Dominik, Kuemmerle-Deschner Jasmin
Department of Pediatrics I, University of Tuebingen, Tuebingen, Germany.
Department of Pediatrics I, University of Tuebingen, Tuebingen, Germany.
Clin Immunol. 2015 Mar;157(1):56-64. doi: 10.1016/j.clim.2015.01.003. Epub 2015 Jan 14.
Cryopyrin-associated periodic syndromes (CAPS) are characterized by recurrent episodes of systemic inflammation caused by mutations in the NLRP3 gene. Besides confirmed pathogenic NLRP3 mutations, patients with CAPS-like symptoms frequently show low penetrance variants in NLRP3. The disease relevance of these variants is inconsistent. In this study, we investigated if an inflammasome activation assay differentiates between patients with confirmed pathogenic CAPS mutations, patients with low penetrance NLRP3 variants (V198M and Q703K) and healthy controls. The release of mature IL-1β, IL-18, and caspase-1 into cell culture supernatants after 4h of inflammasome stimulation was significantly increased in patients with confirmed pathogenic CAPS mutations compared to low penetrance NLRP3 variants and controls. IL-1β secretion in CAPS patients correlated with disease severity. This inflammasome activation assay differentiates between autoinflammation patients with confirmed pathogenic CAPS mutations and patients with low penetrance NLRP3 variants, and points towards alternative pathophysiological mechanisms in low penetrance NLRP3 variants.
冷吡啉相关周期性综合征（CAPS）的特征是由NLRP3基因突变引起的全身性炎症反复发作。除了已确认的致病性NLRP3突变外，有CAPS样症状的患者在NLRP3中经常出现低外显率变异。这些变异与疾病的相关性并不一致。在本研究中，我们调查了炎性小体激活试验是否能区分确诊为致病性CAPS突变的患者、具有低外显率NLRP3变异（V198M和Q703K）的患者以及健康对照。与具有低外显率NLRP3变异的患者和对照相比，炎性小体刺激4小时后，确诊为致病性CAPS突变的患者细胞培养上清液中成熟IL-1β、IL-18和半胱天冬酶-1的释放显著增加。CAPS患者的IL-1β分泌与疾病严重程度相关。这种炎性小体激活试验能够区分确诊为致病性CAPS突变的自身炎症患者和具有低外显率NLRP3变异的患者，并指出低外显率NLRP3变异中存在其他病理生理机制。
