MHC class II sequences of susceptibility and protection in Mexicans with autoimmune hepatitis.
OBJECTIVE
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.
Department of Immunogenetics, Instituto Nacional de Diagnóstico y Referencia Epidemiológicos, SSA, Mexico DF, Mexico.
M N
MN
Vázquez-García
C
C
Aláez
A
A
Olivo
H
H
Debaz
E
E
Pérez-Luque
A
A
Burguete
S
S
Cano
G
G
de la Rosa
N
N
Bautista
A
A
Hernández
J
J
Bandera
L F
LF
Torres
D
D
Kershenobich
F
F
Alvarez
C
C
Gorodezky
D000328:Adult; D004198:Disease Susceptibility; D000939:Epitopes / Q000235:genetics; D005260:Female; D005802:Genes, MHC Class II; D006681:HLA-D Antigens / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D019693:Hepatitis, Autoimmune / Q000235:genetics* / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007113:Immunity, Innate; D007198:Indians, North American / Q000235:genetics; D008297:Male; D008800:Mexico; D016133:Polymerase Chain Reaction / Q000379:methods; D018807:Polymorphism, Single-Stranded Conformational; D012016:Reference Values; D012044:Regression Analysis; D044465:White People / Q000235:genetics
D000939:Epitopes; D006681:HLA-D Antigens; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553505:HLA-DRB1*04:01 antigen