Autoimmune Hepatitis and HLA DRB1 alleles

ROSSI M; RACCA L; MORENO J; ABRAHAM N; COTORRUELO C; BIONDI C; RACCA A; GARCÍA BORRÁS S

Buenos Aires

Congreso; 1st French-Argentine Immunology Congress. LVIII Reunión Annual de la Sociedad Argentina de Inmunología; 2010

Sociedad Argentina de Inmunología

Although the pathogenesis of Autoimmune Hepatitis (AIH) is not completely known, the susceptibility is determined in part by a gene or genes linked to the region HLA Class II. It has a genetic background associated with different HLA DRB1 alleles depending on the ethnic group. The aim of this study was to investigate the contribution of the HLA-DRB1 alleles in development of AIH in Rosario, Argentina. We studied 47 unrelated individuals with diagnostic of AIH and a control group (n= 81) of non-related healthy individuals. Genomic DNA was extracted from peripheral blood using the CTAB method. The alleles were tested for HLA class II genotyping using PCR-SSP. Absence or presence of PCR products was visualized by agarose gel electrophoresis. Differences in the distribution of HLA-DRB1 alleles between patients and controls were analyzed by or Pearson’s 2-test with Yates correction or Fisher’s exact test. Odds ratios (RO) were calculated. The results in the patients with AIH, demonstrated that the highest frequencies corresponded to the following alleles: DRB1*0401 (21.28), DRB1*0101 (13.83), DRB1*0701 (11.70), DRB1*0301 (9.18) y DRB1*1301 (8.51). In controls the most prevalent alleles were: DRB1*0701 (14.20), DRB1*1103 (12.96), DRB1*0808 (12.35), DRB1*1303 (9.26) y DRB1*1101 (8.2). Our results show that the HLA-DRB1*0301 (RO=35.55) HLA-DRB1*0101 (RO=5.04) and HLA-DRB1*0401 (RO=5.98), can be considered as predisposing factors for the development of AIH. By contrast, HLA-DRB1*0808 (RO=0.036), HLA-DRB1*1103 (RO=0.035) and HLA-DRB1*1303 (RO=0.05) alleles were less frequent among patients (p<0.001) and hence more involved in disease resistance. These findings suggest that the polymorphism of HLA-DRB1 contributes to the diverse spectrum of immune responses observed in AIH. The HLA-DRB1 alleles could either act alone or in combination with other genes to confer differential susceptibility and protection in this autoimmune pathology.