Manabe K, Hibberd M L, Donaldson P T, Underhill J A, Doherty D G, Demaine A G, Mieli-Vergani G, Eddleston A L, Williams R
Institute of Liver Studies, King's College Hospital, London, England.
Gastroenterology. 1994 May;106(5):1321-5. doi: 10.1016/0016-5085(94)90025-6.
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.
TCR constant beta (C beta) 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.
A significant increase in the frequency of homozygous status for the 10-kilobase/Bgl II of the TCR C beta 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 C beta 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).
The present findings provide evidence that genetic susceptibility to AIH may be determined by both the TCR C beta genes and HLA genes and that the genotype of the TCR C beta may be one of the factors in influencing the age at onset of disease.
背景/目的：自身免疫性肝炎的易感性与HLA A1 - B8 - DR3和DR4相关。T细胞抗原受体（TCR）是自身免疫性疾病遗传易感性的候选因素，因为它们在HLA分子的背景下识别肽抗原。本研究的目的是调查TCR胚系多态性在自身免疫性肝炎易感性中的可能作用。
采用限制性片段长度多态性分析，对60例无亲缘关系的北欧白人自身免疫性肝炎患者和190例种族和地理匹配的健康对照者进行TCR恒定β（Cβ）区域多态性研究。
与对照组相比，患者中TCR Cβ的10千碱基/Bgl II纯合状态频率显著增加（42%对21%；校正P值[Pc]<0.0075；相对风险[RR]=2.8）。这种差异在无HLA - DR3和DR4的患者中更为明显（50%对14%；Pc<0.015；RR = 6.1）。此外，30岁前出现HLA - DR3的早发型患者中TCR Cβ的杂合性显著降低（12%对48%；Pc<0.03；RR = 0.16）。
本研究结果提供了证据，表明自身免疫性肝炎的遗传易感性可能由TCR Cβ基因和HLA基因共同决定，且TCR Cβ的基因型可能是影响疾病发病年龄的因素之一。
