RESUMO
We have previously reported a strong association between HLA-DRB1*1301 and type 1 pediatric autoimmune hepatitis (PAH) and between HLA-DR*0405 and adult autoimmune hepatitis (AAH). Because human killer cell immunoglobulin-like receptors are known to be associated with susceptibility to autoimmune diseases, we investigated the frequencies of HLA-A, B, C, DRB1 and KIR genes in 144 type 1 PAH and 86 AAH patients, which were compared with 273 healthy controls. We demonstrated in PAH the increased frequency of the functional form of KIR2DS4-Full Length (KIR2DS4-FL), which in combination with HLA-DRB1*1301 revealed a strong synergistic effect (odds ratio=36.5). PAH-KIR2DS4-FL+ subjects have shown an increased frequency of their putative HLA-C*02, 04 and 06 ligands. KIR analysis of PAH also revealed a decreased frequency of KIR2DL2 gene and its ligand. In contrast, AAH cases have shown a weaker increased frequency of KIR2DS4-FL, a lack of synergistic effect with HLA class II antigens and a moderate association with HLA-DRB1*0405. Of note, we demonstrated that liver T cells have a unique pattern of KIR expression. These results show a KIR gene involved in autoimmune hepatitis and suggest a stronger genetic influence for the early onset type I autoimmune hepatitis.
Assuntos
Alelos , Antígenos HLA/genética , Hepatite Autoimune/genética , Receptores KIR/genética , Adulto , Estudos de Casos e Controles , Feminino , Hepatite Autoimune/diagnóstico , Humanos , Masculino , Polimorfismo GenéticoRESUMO
UNLABELLED: Hepatitis A Virus (HAV) infection has been proposed as a possible trigger of autoimmune hepatitis type I. We have previously reported the presence of anti-actin antibodies en protracted hepatitis A. At present the presence of anti-actin antibodies in acute uncomplicated hepatitis A is unknown. The aim of this study was to evaluate the incidence and persistence of anti-actin antibodies un children with acute hepatitis A. MATERIALS AND METHODS: 38 patients, 21 female and 17 male, with mean age of 6.5 years (range 2-13 years) were included. All patients were anti HAV IgM positive. The patients were clinically controlled and laboratory determinations such as ALT/AST, gammaglobulin, gamma GT, nuclear, smooth muscle (anti-actin specificity) and liver-kidney-microsome type I (anti-LKM) antibodies, were evaluated at admission and at the first, third and fifth month. Anti-actin antibodies were determined by indirect immunofluorescense (IIF) on rat kidney, stomach and liver sections and also on monolayers of cultured fibroblasts. Titers higher than 1/40 were considered positive. RESULTS: 18 patients (47.3%) were anti-actin positive in the first determination (titers 1/40 and 1/80). In 4 patients (12.9%) these antibodies remained positive up to one month. All patients were negative 5 months after the onset of illness. ANA and anti-LKM were negative in all cases. CONCLUSIONS: 1) This data demonstrate the presence of anti-actin antibodies in children with uncomplicated HAV hepatitis. 2) The antibodies remained positive for a short period of time. 3) Titers were lower than in autoimmune hepatitis type I. 4) Taken together these results suggest that anti-actin antibodies would be an expression of non specific stimulation of lymphocyte B.