T-CELL RECEPTOR CONSTANT BETA GERMLINE GENE POLYMORPHISMS AND SUSCEPTIBILITY TO AUTOIMMUNE HEPATITIS

Background/Aims: Susceptibility to autoimmune hepatitis is associated with HLA A1-B8-DR3 and DR4. T-Cell antigen receptors (TCR) are candidates for genetic susceptibility to autoimmune diseases because they recognize peptide antigens in the context of HLA molecules. The aim of this study was to investigate the possible role of TCR germline polymorphisms in susceptibility to autoimmune hepatitis. Methods: TCR constant β (Cβ) region polymorphisms were investigated using restriction fragment length polymorphism analysis in 60 unrelated northern European White patients with autoimmune hepatitis and 190 racially and geographically matched healthy controls. Results: A significant increase in the frequency of homozygous status for the 10-kilobase/Bgl II of the TCR Cβ was found in the patients compared with controls (42% vs. 21%; corrected P value [Pc] < 0.0075; relative risk [RR] = 2.8). This difference was more pronounced in patients without HLA-DR3 and DR4 (50% vs. 14%; Pc < 0.015; RR = 6.1). Furthermore, heterozygosity for TCR Cβ was significantly decreased in early-onset patients presenting with HLA-DR3 before 30 years of age (12% vs. 48%; Pc < 0.03; RR = 0.16). Conclusions: The present findings provide evidence that genetic susceptibility to AIH may be determined by both the TCR Cβ genes and HLA genes and that the genotype of the TCR Cβ may be one of the factors in influencing the age at onset of disease. © 1994.