HLA-DRB1 allele distribution in polymyalgia rheumatica and giant cell arteritis: influence on clinical subgroups and prognosis.
OBJECTIVE
To evaluate HLA-DRB1 associations in patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) in the Spanish population, especially those alleles that include the disease-linked sequence motif DRYF (positions 28 to 31 of the HVR2).


METHODS
We performed a PCR based HLA-DRB1 genotyping in 89 PMR patients, 44 GCA patients, and 99 unrelated healthy controls from the same geographic area.


RESULTS
We did not find any significant difference between the whole group of PMR/GCA patients (n = 133) compared with the healthy controls with the exception of a lower frequency of HLA-DRB1*0405 in the patient group (odds ratio [OR], 0.1 [CI0.02 to 1.2]; P =.04). The distribution of DRB1 alleles was very similar between PMR patients and controls. However, DRB1*0401 (OR, 3.1 [1.1 to 8.6]; P =.02) and DRB1*0404 (OR, 3.5 [0.97 to 12.9]; P =.04) were overrepresented in patients with GCA compared with the control group. DRB1*04 (OR, 1.9 [0.96 to 3.8]; P =.06), especially *0401 (OR, 2.8 [1 to 7.7]; P =.04), and DRB1*07 (OR, 2.3 [1.2 to 4.6]; P =.01) were more frequent in GCA than in PMR. Frequency of the DRYF 28-31 motif was similar among GCA (79.5%), PMR (89.9%), and controls (87.9%) and did not confer any significant risk of the development of systemic vasculitis. We also compared the DRB1 allele distribution in patients with classic PMR (n = 58) and those with an erythrocyte sedimentation rate (ESR) <40 mm/hour (n = 31). Patients with classic PMR expressed DRB1*07 less frequently (OR, 0.4 [0.1 to 1]; P =.04) and had a higher frequency of the DRYF 28-31 motif (94.8% vs 80.6%; P =.03) than patients with ESR < 40. Within the GCA group, DRB1 alleles were not predictive for the development of severe ischemic complications. However, the development of relapses in patients with PMR was associated with a higher frequency of DRB1*09 (5.6% vs 0%; P =.04).


CONCLUSIONS
Our data suggest that the HLA-DRB1 alleles associated with susceptibility for developing PMR and GCA are different. Whether PMR with low ESR represents a different clinical subset of the disease should be clarified in a larger sample of patients. HLA-DRB1 genes might predict the presence of relapses in PMR, but they do not seem to be indicators of severe disease in GCA patients.
Division of Rheumatology, Hospital Universitario Marqués de Valdecilla, Facultad de Medicine, Universidad de Cantabria, Cantabria, Spain. vmartinezt@medynet.com
Víctor M
VM
Martínez-Taboda
M Jose
MJ
Bartolome
Marcos
M
Lopez-Hoyos
Ricardo
R
Blanco
Cristina
C
Mata
Jaime
J
Calvo
Alfonso
A
Corrales
Vicente
V
Rodriguez-Valverde
D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005828:Genetics, Population; D013700:Giant Cell Arteritis / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D015994:Incidence; D008297:Male; D011111:Polymyalgia Rheumatica / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D011336:Probability; D011379:Prognosis; D012720:Severity of Illness Index; D017678:Sex Distribution; D013030:Spain / Q000453:epidemiology
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553505:HLA-DRB1*04:01 antigen