For a study, researchers sought to examine the theory that proinflammatory genes differ genetically between patients and controls regarding how they react to viral stimuli in autoimmune hepatitis (AIH type I).

The intrahepatic gene expression of patients with type I AIH (n = 24, aged 9-30 years; referred to as the AIH group later) and controls (n = 21, age 4–25 years) was compared. Complementary DNA (cDNA) libraries created from total RNA extracted from formalin-fixed paraffin-embedded (FFPE) liver biopsy tissues were subjected to RNA sequencing. The levels of gene expression were measured, and the functions of the genes with variable expression were examined. The databases PANTHER and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for pathway analysis. The remaining sequences were mapped to the whole set of viral genomes in the RefSeq database.

Using differential gene analysis, 181 genes with significantly different expression levels were found (136 upregulated in the AIH group). In the AIH group, there was an upregulation of autoimmune pathway genes such as CD19 and CD20, which are crucial for the regulation and maturation of B cells, as well as CD8 and LY9, which are associated with T-cells. CXCL10, a gene hypothesized to be linked to the severity and development of AIH, complement genes (C1QA, C1QB, and C1QC), and human leucocyte antigen (HLA) genes (HLA-DRB1, HLA-DRA, HLA-B, and HLA-C) were all shown to be increased in samples from the AIH group. No particular viral etiologies were discovered.

Unbiased next-generation sequencing and differential gene expression analysis of the AIH group have not only strengthened the case for the involvement of B cells in the pathogenesis and treatment of AIH, but have also identified CXCL10 (anti-CXCL10) and several genes associated with the complement system as potential new therapeutic targets.