HLA-DRB1 allele distribution in polymyalgia rheumatica and giant cell arteritis: influence on clinical subgroups and prognosis
Víctor M Martínez-Taboda1, M Jose Bartolome, Marcos Lopez-Hoyos
1Division of Rheumatology, Hospital Universitario Marqués de Valdecilla, Facultad de Medicine, Universidad de Cantabria, Cantabria, Spain. vmartinezt@medynet.com
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.
Insights
Human leukocyte antigen (HLA)-DRB1 alleles differ in susceptibility to polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). HLA-DRB1 may predict PMR relapses but not severe GCA disease.
Area of Science:
- Immunogenetics
- Rheumatology
- Human Genetics
Background:
- Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are common inflammatory conditions.
- Human leukocyte antigen (HLA) genes, particularly HLA-DRB1, are implicated in autoimmune diseases.
- Specific HLA-DRB1 alleles, including those with the DRYF motif, are associated with disease susceptibility.
Purpose of the Study:
- To investigate HLA-DRB1 associations in Spanish patients with PMR and GCA.
- To identify specific HLA-DRB1 alleles linked to disease susceptibility, focusing on the DRYF motif.
- To explore the predictive value of HLA-DRB1 alleles for disease severity and relapse in PMR and GCA.
Main Methods:
- HLA-DRB1 genotyping using PCR was performed on 89 PMR patients, 44 GCA patients, and 99 healthy controls.
- Allele frequencies were compared between patient groups and controls.
- Association analysis was conducted, including evaluation of the DRYF sequence motif and its correlation with clinical features.
Main Results:
- No significant difference in overall HLA-DRB1 allele frequency was found between PMR/GCA patients and controls, except for a lower frequency of HLA-DRB1*0405 in patients.
- HLA-DRB1*0401 and HLA-DRB1*0404 were overrepresented in GCA patients compared to controls.
- HLA-DRB1*04 (especially *0401) and HLA-DRB1*07 were more frequent in GCA than in PMR. The DRYF motif did not confer significant risk.
- Classic PMR patients had lower frequency of DRB1*07 and higher frequency of the DRYF motif compared to PMR patients with low ESR.
- PMR relapses were associated with a higher frequency of DRB1*09, while HLA-DRB1 alleles did not predict severe GCA complications.
Conclusions:
- Distinct HLA-DRB1 alleles are associated with susceptibility to PMR and GCA.
- PMR with low erythrocyte sedimentation rate (ESR) may represent a distinct clinical subset requiring further investigation.
- HLA-DRB1 genes show potential for predicting PMR relapses but not severe GCA disease.
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