Rapamycin as an Adjunctive Therapy for NLRC4 Associated Macrophage Activation Syndrome

被引：31

作者：

Barsalou, Julie ^{[1
]}

Blincoe, Annaliesse ^{[1
]}

Fernandez, Isabel ^{[2
,3
,4
]}

Dal-Soglio, Dorothee ^{[3
,5
]}

Marchitto, Lorie ^{[3
,4
]}

Selleri, Silvia ^{[4
]}

Haddad, Elie ^{[1
,3
,4
]}

Benyoucef, Aissa ^{[4
]}

Touzot, Fabien ^{[1
,3
,4
]}

机构：

[1] CHU St Justine, Dept Pediat, Dept Immunol Rheumatol, Montreal, PQ, Canada

[2] CHU St Justine, Immunol Lab, Montreal, PQ, Canada

[3] Univ Montreal, Microbiol Infectiol & Immunol Dept, Montreal, PQ, Canada

[4] CHU St Justine, Res Ctr, Montreal, PQ, Canada

[5] Univ Montreal, CHU St Justine, Pathol & Cellular Biol Dept, Montreal, PQ, Canada

来源：

FRONTIERS IN IMMUNOLOGY | 2018年 / 9卷

关键词：

macrophage activation syndrome; NLRC4; inflammasome; mTOR; rapamycin; IL-18; IL-1; beta; AUTOINFLAMMATION; MUTATION; CELLS;

D O I：

10.3389/fimmu.2018.02162

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

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 beta 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.

引用

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