Human leukocyte antigen Class II associations in serum antimitochondrial antibodies (AMA)-positive and AMA-negative primary biliary cirrhosis.
OBJECTIVE
An association of Class II HLA-DR8 antigen is reported in patients with serum antimitochondrial antibodies (AMA)-positive primary biliary cirrhosis (PBC); no information exists as to an association with AMA-negative PBC. We compared the frequency of HLA Class II genes in AMA-positive and AMA-negative PBC patients and healthy controls.


METHODS
Genomic DNA was extracted from the blood of 154 AMA-positive and 26 AMA-negative Caucasian PBC patients and from 216 healthy Caucasian controls and tested for the alleles at two HLA Class II loci, DRbeta1 and DQbeta1.


RESULTS
Higher allele frequencies of HLA-DRbeta1*08 and DQbeta1*04 were found in the AMA-positive PBC patients versus controls (14.9% vs. 6.5%, odds ratio (OR)=3.3, global P=0.03 and 14.4% vs. 6.5%, OR=2.6, global P=0.002). All patients positive for DRbeta1*0801 were positive for the DQbeta1*0402 allele, delta score=22 for AMA-positive patients, 11 for controls. In AMA-negative PBC, the frequency of DRbeta1*08 and DQbeta1*04 was 0%, significantly different from the AMA-positive patients (P=0.05, P=0.05).


CONCLUSIONS
AMA response may identify a group of PBC patients with a distinctive expression of the disease with the response associated with a gene(s) in the class II region of the major histocompatibility complex on the short arm of chromosome 6.
Stone
Julianne
J
Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada.
Wade
Judy A
JA
Cauch-Dudek
Karen
K
Ng
Chang
C
Lindor
Keith D
KD
Heathcote
E Jenny
EJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood*; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics; D059810:HLA-DR Serological Subtypes; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000276:immunology*
D001323:Autoantibodies; D005819:Genetic Markers; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C041559:HLA-DR8 antigen; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II