Functional Assessment of Disease-Associated Pyrin Variants.

Abstract

The pyrin inflammasome detects effectors and toxins that inhibit RhoA GTPases and triggers inflammatory cytokines release and a fast cell death termed pyroptosis. Ancient plague pandemics in the Mediterranean basin have selected in the human population pyrin variants that can trigger an autoinflammatory disease termed familial Mediterranean fever (FMF). In addition, distinct mutations in MEFV, the gene encoding pyrin, cause a different rare autoinflammatory disease termed pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND). As of today, more than 385 MEFV variants have been described although for most of them, whether they are pathogenic variant or benign polymorphism is unknown.Here, we describe different methods using primary human monocytes or engineered monocytic cell lines to functionally characterize MEFV variants, determine their potential pathogenicity, and classify them as either FMF-like or PAAND-like variants.

• Authors: Daria Chirita, Yvan Jamilloux, Thomas Henry, Flora Magnotti
• Journal: Methods in molecular biology (Clifton, N.J.) (Methods Mol Biol) Vol. 2523 Pg. 179-195 ( 2022) ISSN: 1940-6029 [Electronic] United States
• PMID: 35759198 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Inflammasomes
• MEFV protein, human
• Pyrin

Topics

• Familial Mediterranean Fever (diagnosis, genetics)
• Humans
• Inflammasomes (metabolism)
• Monocytes (metabolism)
• Mutation
• Pyrin (genetics)
• Pyroptosis