Cranial and extracranial giant cell arteritis share similar HLA-DRB1 association
Diana Prieto-Peña1, Sara Remuzgo-Martínez2, Javier Gonzalo Ocejo-Vinyals3
1Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, Santander, Spain; Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Bone Diseases of the Musculoskeletal System, IDIVAL, Santander, Spain.
Insights
Giant cell arteritis (GCA) patients with cranial or large-vessel-vasculitis (LVV) phenotypes share similar HLA-DRB1 associations. The HLA-DRB1*04:01 allele is significantly associated with both GCA forms in Spanish populations.
Area of Science:
- Immunogenetics
- Rheumatology
- Vascular Inflammation
Background:
- Giant cell arteritis (GCA) is a systemic vasculitis primarily affecting large arteries.
- Two main phenotypes exist: cranial GCA with ischemic manifestations and large-vessel-vasculitis (LVV)-GCA affecting extracranial arteries.
- The human leukocyte antigen (HLA) system, particularly HLA-DRB1, is implicated in GCA pathogenesis.
Purpose of the Study:
- To investigate whether distinct HLA-DRB1 associations exist between GCA patients presenting with typical cranial ischemic manifestations and those with the LVV-GCA phenotype.
- To compare HLA-DRB1 allele frequencies in these GCA subgroups against healthy controls.
Main Methods:
- A case-control study involving 178 patients with cranial GCA, 100 patients with LVV-GCA, and 486 healthy Spanish controls of European ancestry.
- Comparison of HLA-DRB1 phenotype and allele frequencies between the three groups.
Main Results:
- Both GCA subgroups exhibited distinct clinical features, with LVV-GCA patients being younger and more frequently presenting with polymyalgia rheumatica.
- A significant increase in HLA-DRB1*04 phenotype frequency was observed in both cranial GCA (42.1%) and LVV-GCA (46.0%) patients compared to controls (23.5%).
- This association was primarily driven by the HLA-DRB1*04:01 allele in both cranial GCA (20.8%) and LVV-GCA (19.0%) subgroups, showing significantly higher frequencies than in controls (5.3%).
Conclusions:
- Cranial GCA and extracranial LVV-GCA share a similar HLA-DRB1 association.
- The findings suggest a common genetic susceptibility, particularly involving the HLA-DRB1*04:01 allele, for both GCA phenotypes.
Objective:
To determine whether giant cell arteritis (GCA) patients with the typical pattern of cranial ischemic manifestations and those with the extracranial large-vessel-vasculitis (LVV)-GCA phenotype exhibit different HLA-DRB1 association.
Methods:
178 biopsy-proven GCA patients who had cranial ischemic features but no LVV manifestations, 100 patients with LVV-GCA without cranial ischemic manifestations and 486 ethnically matched healthy controls were recruited. All patients and controls were Spanish of European ancestry. We compared HLA-DRB1 phenotype frequencies between the three groups.
Results:
Both GCA subgroups had well-differentiated clinical features. Patients with LVV-GCA were younger (68.0 ± 10.0 years versus 74.0 ± 10.4 years; p < 0.01) and presented more commonly with polymyalgia rheumatica symptoms (81% versus 39.3%; p < 0.01) than those with the classic cranial GCA phenotype. HLA-DRB1*04 phenotype frequency was significantly increased in patients with classic cranial GCA compared to controls (42.1% versus 23.5%, respectively; p < 0.01; odds ratio-OR [95% confidence interval-CI] = 2.38 [1.62-3.47]). This association was mainly due to the HLA-DRB1*04:01 allele (20.8% versus 5.3%, respectively; p < 0.01; OR [95% CI] = 4.64 [2.63-8.26]). HLA-DRB1*04 association was also observed in LVV-GCA patients when compared to controls (46.0% versus 23.5%, respectively; p < 0.01; OR [95% CI] = 2.78 [1.73-4.44]). Similar to cranial GCA, the association was also mainly due to the HLA-DRB1*04:01 allele (19.0% versus 5.3%, respectively; p < 0.01; OR [95% CI] = 4.15 [2.06-8.19]). Cranial and LVV-GCA patients did not exhibit HLA-DRB1 allele differences.
Conclusion:
Cranial and extracranial LVV-GCA share similar HLA-DRB1 association.
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