Unusual DQA-DR haplotypes in rheumatoid vasculitis.
DQA and DQB variants and HLA haplotypes were defined in Caucasian subjects with rheumatoid arthritis (RA), in a rheumatoid subset characterized clinically by extra-articular features of major vasculitis, and in controls. DQ variants were defined using a panel of sequence specific oligonucleotide probes. In RA subjects without extra-articular features the frequency of DQB*0301 was significantly increased but this was secondary to the main association with DR4. In rheumatoid vasculitis by contrast, DQB*0302 rather than DQB*0301 was increased in frequency, in addition to an increase of C4A null alleles. Family studies showed that DR4 negative haplotypes had an increased frequency of unusual DR-DQA combinations as compared to other rheumatoid subsets. These findings are in keeping with the concept that genes within the MHC other than DR4 have a disease-modifying role in rheumatoid subsets. HLA haplotypes were defined in a family where the proband has RA and Felty's syndrome and an affected sister has rheumatoid vasculitis. These siblings share a DR4 bearing haplotype typing for DQB*0301, and the sister with rheumatoid vasculitis has a DR4 negative haplotype carrying a C4A null allele and an unusual DR-DQA combination.
Hillarby
M C
MC
University of Manchester, Centre for Rheumatic Diseases, Hope Hospital, Salford.
Ollier
W E
WE
Davis
M
M
Davidson
J
J
Sanders
P A
PA
Grennan
D M
DM
D001172:Arthritis, Rheumatoid / Q000150:complications / Q000235:genetics* / Q000276:immunology*; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000276:immunology; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010375:Pedigree; D014657:Vasculitis / Q000150:complications / Q000235:genetics* / Q000276:immunology*
D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C057615:HLA-DQbeta antigen; D006684:HLA-DR Antigens; D015345:Oligonucleotide Probes; D004247:DNA