Journal of hepatology · 1998
MHC class II sequences of susceptibility and protection in Mexicans with autoimmune hepatitis.
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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
Аннотация
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, (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 DQB1*0301 was also detected (chi2Y=8.21, pc=0.04). Analysis of subgroups according to age at onset showed an association with DRB1*0404 (chi2Y=4.31, p=0.04) in patients with late onset (after 30 years), while DQA1*0501 (chi2Y=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 populations 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 findings are relevant in determining which peptides in the liver are targets for T cells.
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, (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 DQB1*0301 was also detected (chi2Y=8.21, pc=0.04). Analysis of subgroups according to age at onset showed an association with DRB1*0404 (chi2Y=4.31, p=0.04) in patients with late onset (after 30 years), while DQA1*0501 (chi2Y=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 populations 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 findings are relevant in determining which peptides in the liver are targets for T cells.
Предметные рубрики MeSH
AdultDisease SusceptibilityEpitopesFemaleGenes, MHC Class IIHLA-D AntigensHLA-DQ AntigensHLA-DQ alpha-ChainsHLA-DQ beta-ChainsHLA-DR AntigensHLA-DRB1 ChainsHepatitis, AutoimmuneHistocompatibility TestingHumansImmunity, InnateIndians, North AmericanMaleMexicoPolymerase Chain ReactionPolymorphism, Single-Stranded ConformationalReference ValuesRegression AnalysisWhite People