Autoantibody and Human Leukocyte Antigen Profiles in Children With Autoimmune Liver Disease and Their First‐Degree Relatives

ABSTRACT Objective: Familial clustering of juvenile autoimmune liver disease (AILD), including autoimmune hepatitis and autoimmune sclerosing cholangitis (ASC), is rare, despite a high prevalence of autoimmune disorders in AILD families. Methods: To investigate this discrepancy, we measured autoantibodies diagnostic for AILD, anti‐nuclear, anti‐smooth muscle, anti‐liver kidney microsomal type 1, anti‐liver cytosol type 1, and anti‐soluble liver antigen antibodies, and human leukocyte antigen profiles in 31 patients and 65 of their first‐degree relatives (FDR). The autoantibody profile was compared with that of 42 healthy subjects (HS). Results: Autoantibodies were detected in 71% (22/31) patients. Anti‐nuclear antibody or anti‐smooth muscle antibody were present in 4/65 FDR (6.2%). HS were negative for all autoantibodies. The frequencies of homozygous HLA DRB1*0301 (DR3) genes and haplotype A1‐B8‐DR3 were higher in the patients (25% and 43%) than in FDR (9% and 27%) and HS (0% and 16%). The frequencies of disease‐protective genes DR4 and/or DR15 were lower in the patients (25%) than in FDR (42%) and HS (42%). Only 1 family contained 2 patients with AILD, 1 with ASC and 1 with primary sclerosing cholangitis. Both patients possessed A1‐B8‐DR3 genes, the ASC being homozygous and the primary sclerosing cholangitis heterozygous. Six FDR had nonhepatic autoimmune disorders, none being autoantibody positive. Conclusions: Homozygosity for DR3 plays a major role in the predisposition to juvenile AILD. Diagnostic autoantibodies for AILD are rare among patients' FDR and not linked to clinical manifestation of AILD.