Related Experiment Video
Updated: Apr 18, 2026
Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages
Published on: May 21, 2018
A functional inflammasome activation assay differentiates patients with pathogenic NLRP3 mutations and symptomatic
Nikolaus Rieber1, Alina Gavrilov1, Laura Hofer1
1Department of Pediatrics I, University of Tuebingen, Tuebingen, Germany.
Abstract:
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.
