HLA-DRB1 alleles in polymyalgia rheumatica, giant cell arteritis, and rheumatoid arthritis.
OBJECTIVE
Immunogenetic analysis has demonstrated that giant cell arteritis (GCA) and rheumatoid arthritis (RA) are associated with 2 different domains of the HLA-DR4 molecule. The present study was undertaken to evaluate whether polymyalgia rheumatica (PMR) immunogenetically resembles GCA or RA and to determine whether expression of HLA-DRB1 alleles can be used to detect heterogeneity among PMR patients.


METHODS
Forty-six patients with PMR, 52 with GCA, 122 with seropositive RA, and 72 normal individuals were genotyped for HLA-DRB1 alleles by allele-specific amplification and subsequent oligonucleotide hybridization.


RESULTS
The HLA-DRB1*04 allele was the most frequent among PMR patients (67%). While the expression of allelic variants of the HLA-DR4 family was restricted to HLA-DRB1*0401 and *0404/8 in RA patients, all HLA-DRB1*04 alleles, including B1*0402 and B1*0403, were represented in the PMR group. The distribution of HLA-DRB1 alleles among HLA-DRB1*04 negative patients was similar in those with PMR and those with GCA, and could be distinguished from that in RA patients. In particular, HLA-DRB1*01 alleles, which were found in most HLA-DRB1*04 negative RA patients, were underrepresented in patients with PMR and GCA.


CONCLUSIONS
The distribution of HLA-DRB1 alleles in PMR resembles that found in GCA. PMR and GCA share the associated sequence polymorphism encoded by the second hypervariable region (HVR) of the HLA-DRB1 gene. The HLA-DRB1 association of PMR and GCA can be distinguished from that of RA, which is linked to a sequence motif in the third HVR of DRB1 alleles. The differential role of distinct domains on HLA-DR molecules suggests that multiple biologic functions are regulated by these molecules and that they contribute differently to disease mechanisms. The similarities in the distribution of HLA-DRB1 alleles in PMR and GCA indicates that HLA-DRB1 alleles are not predictive for progression of PMR to the vasculitic lesions that are pathognomonic for GCA.
Weyand
C M
CM
Mayo Clinic and Foundation, Rochester, Minnesota 55905.
Hunder
N N
NN
Hicok
K C
KC
Hunder
G G
GG
Goronzy
J J
JJ
D000368:Aged; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation; D013700:Giant Cell Arteritis / Q000235:genetics* / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D008297:Male; D011111:Polymyalgia Rheumatica / Q000235:genetics* / Q000276:immunology
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553505:HLA-DRB1*04:01 antigen; D000949:Histocompatibility Antigens Class II