A functional inflammasome activation assay differentiates patients with pathogenic NLRP3 mutations and symptomatic patients with low penetrance variants

A functional inflammasome activation assay differentiates patients with pathogenic NLRP3 mutations and symptomatic patients with low penetrance variants

Copyright © 2015 Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 157(2015), 1 vom: 01. März, Seite 56-64
1. Verfasser: Rieber, Nikolaus (VerfasserIn)
Weitere Verfasser: Gavrilov, Alina, Hofer, Laura, Singh, Anurag, Öz, Hasan, Endres, Theresa, Schäfer, Iris, Handgretinger, Rupert, Hartl, Dominik, Kuemmerle-Deschner, Jasmin
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2015
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Comparative Study Journal Article Research Support, Non-U.S. Gov't Autoinflammation CAPS IL-1β NLRP3 TNF-α Variants Carrier Proteins mehr... Inflammasomes NLR Family, Pyrin Domain-Containing 3 Protein NLRP3 protein, human
Beschreibung
Zusammenfassung:Copyright © 2015 Elsevier Inc. All rights reserved.
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
Beschreibung:Date Completed 18.05.2015
Date Revised 25.11.2016
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2015.01.003