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Mannose-binding lectin variant alleles and HLA-DR4 alleles are associated with giant cell arteritis
Soren Jacobsen1, Bo Baslund, Hans Ole Madsen
1Department of Rheumatology, Hvidovre Hospital, Copenhagen, Denmark. sj@dadlnet.dk
Objective:
To determine whether variant alleles of the mannose-binding lectin (MBL) gene causing low serum concentrations of MBL and/or polymorphisms of HLA-DRB1 are associated with increased susceptibility to polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) or particular clinical phenotypes of PMR/GCA.
Methods:
MBL and HLA-DRB1 alleles were determined by polymerase chain reaction in 102 Danish patients with PMR (n = 37) or GCA (n = 65). Two hundred fifty and 193 healthy individuals served as controls for MBL and HLA genotyping, respectively.
Results:
The prevalence of MBL variant alleles in controls, patients with PMR only, and patients with GCA was 37, 32, and 53% (p = 0.01), respectively. HLA-DRB1*04 was found in 47% of patients with PMR only and in 54% of patients with GCA, which differed significantly from the 35% found in controls (p = 0.01). HLA-DR4 alleles were not associated with any clinical phenotypes of PMR/GCA, whereas MBL variant alleles were associated with cranial arteritis, high erythrocyte sedimentation rate, and low B-hemoglobin.
Conclusion:
We found MBL variant alleles and HLA-DR4 alleles to be weak susceptibility markers for GCA. In patients with PMR/GCA, MBL variant alleles were associated with signs of increased inflammatory activity and clinical signs of arteritic manifestations. This was not found for HLA-DR4 alleles. These findings indicate that HLA-DR4 and MBL are contributing to the pathophysiology of GCA at different levels in the disease process.
Insights
Mannose-binding lectin (MBL) variant alleles are associated with increased inflammatory activity in polymyalgia rheumatica/giant cell arteritis (PMR/GCA). HLA-DR4 alleles are weak susceptibility markers for GCA but not linked to specific clinical features.
Area of Science:
- Immunogenetics
- Rheumatology
- Molecular Biology
Background:
- Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are inflammatory conditions with unknown precise etiologies.
- Genetic factors, including mannose-binding lectin (MBL) and HLA-DRB1 gene polymorphisms, are investigated for their role in disease susceptibility and phenotype.
Purpose of the Study:
- To investigate the association between MBL gene variant alleles and HLA-DRB1 polymorphisms with susceptibility to PMR and GCA.
- To determine if these genetic factors correlate with specific clinical phenotypes in PMR/GCA patients.
Main Methods:
- Genotyping for MBL and HLA-DRB1 alleles was performed using polymerase chain reaction (PCR).
- Study included 102 Danish patients diagnosed with PMR or GCA and healthy control groups for comparison.
Main Results:
- MBL variant alleles were more prevalent in GCA patients (53%) compared to controls (37%) and PMR patients (32%).
- HLA-DRB1*04 and HLA-DR4 alleles were found more frequently in PMR/GCA patients (47-54%) than in controls (35%).
- MBL variant alleles correlated with cranial arteritis, elevated erythrocyte sedimentation rate, and low hemoglobin, unlike HLA-DR4.
Conclusions:
- MBL variant alleles and HLA-DR4 alleles are identified as weak susceptibility markers for GCA.
- MBL variant alleles are linked to heightened inflammatory activity and arteritic manifestations in PMR/GCA patients.
- Findings suggest MBL and HLA-DR4 influence GCA pathophysiology through distinct mechanisms.