The current treatment of Type-I Autoimmune Hepatitis sensitizes the innate immune system in the liver of adult patients

FLORENCIA FERRO; INZAUGARAT ME; CECILIA GARCPIA; ALEGRE NADIA S.; CUARTEROLO M; CRISTINA GALLOPO; GONZALEZ BALLERGA E; DARUICH J; SORDA JA; A. C. CHERÑAVSKY

Mar del Plata

Congreso; LIX Reunión de la Sociedad Agentina de Inmunología; 2014

SAI

Background: Prednisone alone or in a lower dose combined with azathioprine is the standard treatment of type I Autoimmune Hepatitis (AIH). AIH shows a chronic course with relapses after discontinuation of the immunosuppressive therapy. We have previously demonstrated that some pro-inflammatory cytokines and chemokines remain expressed in the liver of pediatric patients despite of the treatment. Expression of some Inflammasome (Inf) -associated genes has been recently demonstrated in experimental AIH. Objective: to evaluate the involvement of NLRP3 Inf in adult (A) patients with AIH at diagnosis (AIH-A) and the modulation of NLRP3-associated genes in adults and pediatric (P) patients in biochemical remission achieved after treatment with corticosteroids (AIH-AT, AIH-PT). Methods: hepatic biopsies from 6 AIH-P, 7 AIH-A, 7 AIH-PT, 7 AIH-AT and liver tissue from 7 cadaveric adult donors as control livers (Co) were processed for gene expression assessment. NLRP3, ASC, caspase-1 (casp-1), IL-1, IL-18 and GAPDH mRNA expression was analyzed by Real-Time PCR. Fold-change values were calculated using the 2-ΔΔCt method. Data were analyzed by Kruskal-Wallis with Dunn´s multiple comparison post-test (adults) and Mann-Whitney (pediatric patients). Results: Expression of NLRP3 is increased in AIH-A (p