Somatic mosaic NLRP3 mutations and inflammasome activation in late-onset chronic urticaria.

08:00 EDT 9th September 2019 | BioPortfolio

Summary of "Somatic mosaic NLRP3 mutations and inflammasome activation in late-onset chronic urticaria."

Chronic urticaria is a common skin disorder with heterogeneous causes. In the absence of physical triggers, chronic urticarial rash is called idiopathic or spontaneous. The objective of the current study was to identify the molecular and cellular bases of a disease condition displayed by two unrelated patients aged over 60 years who presented for two decades with a chronic urticaria resistant to standard therapy which occurred in the context of systemic inflammation not triggered by cold. In both patients, a targeted sequencing approach using a next generation technology identified somatic mosaic mutations in NLRP3, a gene encoding a key inflammasome component. The study of several patients' cell types showed that despite the late onset of the disease, NLRP3 mutations were not found to be restricted to myelomonocytic cells. Rather, the data obtained strongly suggested that the mutational event occurred very early, during the embryonic development. As shown by functional studies, the identified mutations -an in-frame deletion and a recurrent NLRP3 missense mutation- have a gain-of-function effect on NLRP3-inflammasome activation. Consistently, a complete remission was obtained in both patients with anti-interleukin 1 receptor antagonists. This study unveils that in late-onset chronic urticaria, the search for autoinflammatory markers and somatic mosaic NLRP3 mutations may have important diagnostic and therapeutic consequences.


Journal Details

This article was published in the following journal.

Name: The Journal of investigative dermatology
ISSN: 1523-1747


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