HLA, gut microbiome and hepatic autoimmunity

Front Immunol. 2022 Aug 18:13:980768. doi: 10.3389/fimmu.2022.980768. eCollection 2022.

Abstract

Genetic susceptibility to autoimmune liver diseases is conferred mainly by polymorphisms of genes encoding for the human leukocyte antigens (HLA). The strongest predisposition to autoimmune hepatitis type 1 (AIH-1) is linked to the allele DRB1*03:01, possession of which is associated with earlier disease onset and more severe course. In populations where this allele is very rare, such as in Asia, and in DRB1*03-negative patients, risk of AIH-1 is conferred by DRB1*04, which is associated with later disease onset and milder phenotype. AIH type 2 (AIH-2) is associated with DRB1*07. The pediatric condition referred to as autoimmune sclerosing cholangitis (ASC), is associated with the DRB1*13 in populations of Northern European ancestry. DRB1*1501 is protective from AIH-1, AIH-2 and ASC in Northern European populations. Possession of the DRB1*08 allele is associated with an increased risk of primary biliary cholangitis (PBC) across different populations. DRB1*03:01 and B*08:01 confer susceptibility to primary sclerosing cholangitis (PSC), as well as DRB1*13 and DRB1*15 in Europe. The hepatic blood supply is largely derived from the splanchnic circulation, suggesting a pathophysiological role of the gut microbiome. AIH appears to be associated with dysbiosis, increased gut permeability, and translocation of intestinal microbial products into the circulation; molecular mimicry between microbial and host antigens may trigger an autoaggressive response in genetically-predisposed individuals. In PBC an altered enteric microbiome may affect intestinal motility, immunological function and bile secretion. Patients with PSC have a gut microbial profile different from health as well as from patients with inflammatory bowel disease without PSC.

Keywords: AIH; autoimmune hepatitis; gut microbiome; human leucocyte antigen (HLA); primary biliary cholangitis (PBC); primary sclerosing cholangites (PSC).

Publication types

  • Review

MeSH terms

  • Autoimmunity / genetics
  • Child
  • Cholangitis, Sclerosing* / genetics
  • Gastrointestinal Microbiome* / genetics
  • Genetic Predisposition to Disease
  • HLA Antigens / genetics
  • HLA-DRB1 Chains* / genetics
  • Hepatitis, Autoimmune* / genetics
  • Humans

Substances

  • HLA Antigens
  • HLA-DRB1 Chains