AUTHOR=Barsalou Julie , Blincoe Annaliesse , Fernandez Isabel , Dal-Soglio Dorothée , Marchitto Lorie , Selleri Silvia , Haddad Elie , Benyoucef Aissa , Touzot Fabien 

TITLE=Rapamycin as an Adjunctive Therapy for NLRC4 Associated Macrophage Activation Syndrome

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.02162

DOI=10.3389/fimmu.2018.02162

ISSN=1664-3224

ABSTRACT=<p>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 <italic>in vitro</italic> 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 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.</p>