Vázquez-García M N, Aláez C, Olivo A, Debaz H, Pérez-Luque E, Burguete A, Cano S, de la Rosa G, Bautista N, Hernández A, Bandera J, Torres L F, Kershenobich D, Alvarez F, Gorodezky C
Department of Immunogenetics, Instituto Nacional de Diagnóstico y Referencia Epidemiológicos, SSA, Mexico DF, Mexico.
J Hepatol. 1998 Jun;28(6):985-90. doi: 10.1016/s0168-8278(98)80347-4.
BACKGROUND/AIMS: Autoimmune hepatitis has a genetic background associated with different HLA DRB1 alleles depending on the ethnic group. The aim of this study was to analyse the immunogenetics of type I autoimmune hepatitis in Mexicans.
Thirty Mexican Mestizo patients and 175 healthy controls were HLA typed as follows: class I antigens were determined by microlymphocytotoxicity and class II typing was done on DNA samples using PCR-SSO and PCR-SSP for DRB1, DQA1 and DQB1 loci.
A significant association of autoimmune hepatitis with DRB10404 was found, (chi2Y=19.95, pc=0.002, RR=7.71), suggesting the presence of a susceptibility gene located at the DRB1 locus. Resistance was at least partially due to a DQB1 gene, since a significant decrease in DQB10301 was also detected (chi2Y=8.21, pc=0.04). Analysis of subgroups according to age at onset showed an association with DRB10404 (chi2Y=4.31, p=0.04) in patients with late onset (after 30 years), while DQA10501 (chi2Y=5.12, p=0.02) was increased in the early onset group.
The possible mechanism of HLA association is due to "shared epitopes", since DRB10404, and those found in other populations namely, DRB10401, *0405 and 0301 share almost the same sequence at position 67-72 (LLEQRR, R or K at 71). Valine-86 is also relevant to the age at onset because DRB10404 is increased in the patients with an average age at onset of 32. These findings are relevant in determining which peptides in the liver are targets for T cells.
背景/目的：自身免疫性肝炎具有遗传背景，根据种族不同，与不同的人类白细胞抗原DRB1等位基因相关。本研究的目的是分析墨西哥人I型自身免疫性肝炎的免疫遗传学。
对30名墨西哥混血患者和175名健康对照进行HLA分型，具体如下：I类抗原通过微量淋巴细胞毒性测定，II类分型在DNA样本上进行，使用PCR-SSO和PCR-SSP检测DRB1、DQA1和DQB1基因座。
发现自身免疫性肝炎与DRB10404显著相关（卡方Y=19.95，pc=0.002，相对危险度=7.71），提示在DRB1基因座存在一个易感基因。抵抗力至少部分归因于DQB1基因，因为也检测到DQB10301显著减少（卡方Y=8.21，pc=0.04）。根据发病年龄分析亚组，发现发病较晚（30岁以后）的患者与DRB10404相关（卡方Y=4.31，p=0.04），而发病较早组中DQA10501增加（卡方Y=5.12，p=0.02）。
HLA关联的可能机制是由于“共享表位”，因为DRB10404以及在其他人群中发现的DRB10401、0405和0301在67-72位具有几乎相同的序列（LLEQRR，71位为R或K）。缬氨酸-86也与发病年龄相关，因为发病平均年龄为32岁的患者中DRB1*0404增加。这些发现对于确定肝脏中的哪些肽是T细胞的靶标具有重要意义。
