Major histocompatibility complex genes and susceptibility to systemic lupus erythematosus.
Susceptibility to systemic lupus erythematosus is associated with major histocompatibility complex (MHC)--encoded genes. We have used nucleotide sequence analysis to better define the disease-associated MHC alleles. HLA-DR2, DQw1, and especially the rare allele DQ beta 1. AZH confer high relative risk (RR = 14) for lupus nephritis in a Caucasian population of patients. Pilot studies using historical controls suggest that these genes also confer a high risk in non-Caucasian ethnic groups (RR = 24-78). We have found that DR4 is significantly decreased in patients with lupus nephritis. Fifty percent of the patients with lupus nephritis had either the DQ beta 1.1, the DQ beta 1.AZH, or the DQ beta 1.9 alleles. These alleles share amino acid residues that have been predicted to be the contact points for antigen and the T cell receptor. These HLA alleles appear to have a direct role in the predisposition to lupus nephritis, whereas DR4 may have a "protective" effect.
Fronek
Z
Z
Department of Medicine, University of California, San Diego, La Jolla 92093.
Timmerman
L A
LA
Alper
C A
CA
Hahn
B H
BH
Kalunian
K
K
Peterlin
B M
BM
McDevitt
H O
HO
D000483:Alleles; D003165:Complement System Proteins / Q000235:genetics; D004198:Disease Susceptibility; D005809:Genes, Regulator / Q000235:genetics; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D015804:HLA-DR4 Antigen / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D008285:Major Histocompatibility Complex / Q000235:genetics*; D010865:Pilot Projects; D011110:Polymorphism, Genetic / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors
D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C051568:HLA-DQ1 antigen; C057615:HLA-DQbeta antigen; D015804:HLA-DR4 Antigen; D000949:Histocompatibility Antigens Class II; D003165:Complement System Proteins