Absence of DRw15/3 and of DRw15/7 heterozygotes in Caucasian patients with systemic lupus erythematosus.
Polymorphic MHC class II molecules determine immune responsiveness towards pathogens and also contribute to susceptibility or resistance to a number of different autoimmune diseases, including systemic lupus erythematosus (SLE). The HLA-DR and -DQ alleles of 52 patients with SLE were analyzed by serology and, for 42 patients, HLA-DRB1, -B3 and DQB1 allelic polymorphism was determined by oligotyping on PCR-amplified DNA. While we confirm the increase of DR3 (44.2% versus 16% in controls; p less than 0.001) reported by others, we observed a complete absence of DRw15(2)/DR3 and DRw15(2)/DR7 heterozygotes among Caucasian patients. Moreover HLA-DQB1 oligotyping revealed the absence of DQB1*0602/0201 heterozygotes in our panel of Caucasoid SLE patients. Since both DR3 and DR7 haplotypes share the same DQB1*0201-encoded DQ beta chain, and since DRw15 is known to be in linkage disequilibrium with DQA1*0102, it can be predicted that DQA1*0102/DQB1*0201 combinations are absent in Caucasian patients. We therefore propose that a DQA1*0201/DQB1*0201-encoded HLA-DQ trans-dimer formed in these heterozygotes might function as a suppressor-inducer molecule that confers resistance against SLE.
Reinharz
D
D
Départment de médecine, Hôspital Cantonal Universitaire, Switzerland.
Tiercy
J M
JM
Mach
B
B
Jeannet
M
M
D015139:Blotting, Southern; D005784:Gene Amplification; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics*; D059810:HLA-DR Serological Subtypes; D006579:Heterozygote; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D044465:White People / Q000235:genetics*
D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C106559:HLA-DR15 antigen