HLA Associations in pediatric autoimmune liver diseases: Current state and future research initiatives

Abstract

The strongest genetic association with autoimmunity is within chromosome 6p21, where the human leukocyte antigen (HLA) complex resides. This review will focus on the HLA associations within pediatric autoimmune hepatitis, autoimmune sclerosing cholangitis and primary sclerosing cholangitis. In general, there is considerable overlap in HLA genotypes conferring susceptibility to pediatric autoimmune liver diseases, however unique HLA associations and protective HLA genotypes exist. There are numerous areas for future research initiatives in pediatric autoimmune liver diseases and HLA associations with clinical outcomes, autoantigen discovery and novel therapeutics targeting the HLA- autoantigen- T cell pathway will be highlighted.

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“…Numerous factors influence the onset and progression of AIH in children, with high-risk genetic elements playing a pivotal role. Genome-wide association studies (GWAS) have unequivocally linked specific HLA alleles, notably HLA-DRB1 03:01 and HLA-DRB1 07:01, with type 2 AIH [2, 6]. This genetic association underscores the crucial involvement of antigen-presenting cells (APCs) and activated CD4+ T helper cells in the pathogenesis of the disease.…”

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“…Historically, AIH has been thought to be a T cell-driven disease associated with impaired regulatory T cell function and autoreactive T cells ( 28 , 29 ) linked to HLA class II associations ( 30 , 31 ). Thus, T cells are likely to be important for disease onset.…”