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Molecular analysis of HLA-DR polymorphism in polymyalgia rheumatica. Swiss Group for Research on HLA in Polymyalgia
1Division of Rheumatology, University Hospital, Geneva, Switzerland.
Objective:
To analyze by molecular typing possible associations of HLA-DRB1 alleles with polymyalgia rheumatica (PMR) compared to controls and patients with rheumatoid arthritis (RA) in Switzerland.
Methods:
In a multicenter survey, we recruited 100 patients with PMR with and without signs of giant cell arteritis (GCA), 198 with RA, and 200 controls (volunteer bone marrow donors). HLA-DR generic typing was performed by microtiter plate oligotyping and DR4 subtypes analyzed by dot blot hybridization with sequence specific oligonucleotides or by polymerase chain reaction sequence specific primers.
Results:
DR4 and DR1 tended to be increased in PMR, compared to controls (36 vs 30%, p = 0.30; and 19 vs 12%, p = 0.16, respectively). Frequencies of all RA associated DR4 and DR1 subtypes tended to be increased in PMR as well. Frequency of the HLA-DR beta 1 70-74 shared motif (QK/RRAA) was significantly higher in PMR than in controls [50 vs 36%, odds ratio (OR) = 1.8, p = 0.018], although lower than in RA (77 vs 36%, OR = 6.0, p < 0.0001), and slightly out of the range of significance if a Bonferroni correction was applied (p = 0.1). At double dose, this epitope was also increased in PMR, but not significantly (5 vs 2%, OR = 2.6, p = 0.17), while it was markedly augmented in RA (22 vs 2%, OR = 14, p = < 0.0001). In patients with the shared epitope, the frequency of clinical signs of GCA tended to be increased (19 vs 10%, p = 0.25). Frequency of the HLA-DR beta 1 DRYF 28-31 motif was identical in PMR (95%) and controls (93%).
Conclusion:
PMR may be associated with the HLA-DR beta 1 70-74 shared epitope. This association, however, would be much weaker for PMR than for RA, particularly with the shared epitope at double dose. PMR is clearly not associated with the HLA-DR beta 1 DRYF 28-31 motif.
Insights
Polymyalgia rheumatica (PMR) may be linked to the HLA-DR beta 1 70-74 shared epitope, though less strongly than rheumatoid arthritis (RA). This specific epitope is not associated with PMR.
Area of Science:
- Immunogenetics
- Rheumatology
Background:
- Polymyalgia rheumatica (PMR) is an inflammatory condition with unclear etiology.
- Human Leukocyte Antigen (HLA) genes, particularly HLA-DRB1, are implicated in autoimmune diseases.
Purpose of the Study:
- To investigate the association between specific HLA-DRB1 alleles and PMR in a Swiss population.
- To compare these associations with those in patients with rheumatoid arthritis (RA) and healthy controls.
Main Methods:
- A multicenter study involving 100 PMR patients, 198 RA patients, and 200 controls.
- Molecular typing using microtiter plate oligotyping and dot blot hybridization/PCR for HLA-DRB1 alleles and subtypes.
Main Results:
- The HLA-DR beta 1 70-74 shared epitope (QK/RRAA) was significantly more frequent in PMR patients (50%) compared to controls (36%, OR=1.8, p=0.018).
- This association was weaker in PMR than in RA (77%, OR=6.0, p<0.0001).
- No significant association was found between PMR and the HLA-DR beta 1 DRYF 28-31 motif.
Conclusions:
- The HLA-DR beta 1 70-74 shared epitope may be associated with PMR, but the link is considerably weaker than for RA.
- PMR is not associated with the HLA-DR beta 1 DRYF 28-31 motif.