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MHC class II sequences of susceptibility and protection in Mexicans with autoimmune hepatitis

1998; Elsevier BV; Volume: 28; Issue: 6 Linguagem: Inglês

10.1016/s0168-8278(98)80347-4

1600-0641

Miriam Nohemí Vázquez García, C. Aláez, Alessandro Olivo, Debaz Hector, Elva Pérez‐Luque, Ana I. Burguete-García, Silvia Cano, Gabriela de la Rosa, Norma Bautista, Arturo Hernández, José Bandera, Luis Fernando Torres, David Kershenobich, Fernando Álvarez, Clara Gorodezky,

Liver Disease Diagnosis and Treatment

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. Methods: 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. Results: A significant association of autoimmune hepatitis with DRB1*0404 was found, (χ2Y=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 DQB1*0301 was also detected (χ2Y=8.21, pc=0.04). Analysis of subgroups according to age at onset showed an association with DBR1*0404 (χ2Y=4.31, p=0.04) in patients with late onset (after 30 years), while DQA1*0501 (χ2Y=5.12, p=0.02) was increased in the early onset group. Conclusions: The possible mechanism of HLA association is due to "shared epitopes", since DRB1*0404, and those found in other populatios namely, DRB1*0401, *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 DRB1*0404 is increased in the patients with an average age at onset of 32. These findigs are relevant in determining which peptides in the liver are targets for T cells.