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Rapamycin as an Adjunctive Therapy for NLRC4 Associated Macrophage Activation Syndrome.

ABSTRACT: Gain of function (GOF) mutations affecting the inflammasome component NLRC4 are known to cause early-onset macrophage activation syndrome (MAS) and neonatal enterocolitis. Here we report a patient with a NLRC4 GOF mutation presenting with neonatal MAS efficiently treated with a combination of anakinra and rapamycin. Through in vitro studies, we show that rapamycin reduces both IL-1? and IL-18 secretion by the patient's phagocytic cells. The reduction of cytokine secretion is associated with a reduction of caspase-1 activation regardless of the pathogen- or danger-associated molecular patterns triggering the activation of the inflammasome. This study suggests that patients with inherited auto-inflammatory disorders could benefit from an adjunctive therapy with rapamycin.

SUBMITTER: Barsalou J

PROVIDER: S-EPMC6166634 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Rapamycin as an Adjunctive Therapy for NLRC4 Associated Macrophage Activation Syndrome.

Barsalou Julie J Blincoe Annaliesse A Fernandez Isabel I Dal-Soglio Dorothée D Marchitto Lorie L Selleri Silvia S Haddad Elie E Benyoucef Aissa A Touzot Fabien F

Frontiers in immunology 20180924

Gain of function (GOF) mutations affecting the inflammasome component NLRC4 are known to cause early-onset macrophage activation syndrome (MAS) and neonatal enterocolitis. Here we report a patient with a NLRC4 GOF mutation presenting with neonatal MAS efficiently treated with a combination of anakinra and rapamycin. Through <i>in vitro</i> studies, we show that rapamycin reduces both IL-1β and IL-18 secretion by the patient's phagocytic cells. The reduction of cytokine secretion is associated wi ...[more]

PMID: 30319625

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