Association of HLA-DR genes with mild idiopathic adulthood biliary ductopenia

Abstract

OBJECTIVE: Mild idiopathic adulthood ductopenia (MIAD) is an asymptomatic chronic cholestatic liver disease characterized by the loss of interlobular bile ducts in <50% of the portal tracts. Although the underlying cause of MIAD is unknown, the host factors may contribute to the patient’s susceptibility to the disease. The aim of this work was to investigate the immunogenetics in the pathogenesis of MIAD. METHODS: We prospectively studied 22 Caucasian patients with MIAD. Peripheral blood was collected, and HLA-DR typing was performed by polymerase chain reaction with sequence-specific primers followed by sequencing for subtyping. Results were compared with those from 140 age- and sex-matched controls. RESULTS: There was no significant association between HLA-DRB1 alleles and the disease, although a trend was found in MIAD patients with the DRB1∗1502 allele (five of 44 vs four of 280 in controls; p corrected = 0.055; χ 2 = 13.9). Multiple HLA-DRB1 alleles (∗04, ∗11, ∗15) showed increased frequencies in MIAD patients. Further subtyping revealed a motif (positions 25–32 of the β1 chain) present in 17 (77.3%) patients, which was significantly associated with MIAD ( p = 0.049; χ 2 = 3.87). Seven patients (31.8%) and 21 (15%) controls coded for this motif in their two alleles ( p = 0.068; χ 2 = 3.76). Among MIAD patients, those seven had abnormal ALT levels ( p = 0.017) and their γ-glutamyltransferase and ALT values tended to be more increased. CONCLUSIONS: These results provide evidence of an immunogenetic basis of susceptibility to MIAD in Caucasian individuals.