Rapamycin as an Adjunctive Therapy for NLRC4 Associated Macrophage Activation Syndrome.
Front Immunol
; 9: 2162, 2018.
Article
in En
| MEDLINE
| ID: mdl-30319625
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-1ß 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Calcium-Binding Proteins
/
CARD Signaling Adaptor Proteins
/
Macrophage Activation Syndrome
/
Gain of Function Mutation
Type of study:
Risk_factors_studies
Limits:
Female
/
Humans
Language:
En
Journal:
Front Immunol
Year:
2018
Document type:
Article
Affiliation country:
Canada