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HLA-DRB1 alleles associated with polymyalgia rheumatica in northern Italy: correlation with disease severity
C Salvarani1, L Boiardi, V Mantovani
1Servizio di Reumatologia, Arcispedale S Maria Nuova, Reggio Emilia, Italy.
Objective:
To examine the association of HLA-DRB1 alleles with polymyalgia rheumatica (PMR) in a Mediterranean country and to explore the role of HLA-DRB1 genes in determining disease severity.
Methods:
A five year prospective follow up study of 92 consecutive PMR patients diagnosed by the secondary referral centre of rheumatology of Reggio Emilia, Italy was conducted. HLA-DRB1 alleles were determined in the 92 patients, in 29 DR4 positive rheumatoid arthritis (RA) patients, and in 148 controls from the same geographical area by polymerase chain reaction amplification and oligonucleotide hybridisation.
Results:
No significant differences were observed in the frequencies of HLA-DRB1 types and in the expression of HLA-DRB 70-74 shared motif between PMR and controls. The frequency of the patients with double dose of epitope was low and not significantly different in PMR and in controls. No significant differences in the distribution of HLA-DR4 subtypes were observed between DR4+ PMR, DR+ RA, and DR4+ controls. Results of the univariate analysis indicated that an erythrocyte sedimentation rate (ESR) at diagnosis > 72 mm 1st h, the presence of HLA-DR1, DR10, rheumatoid epitope, and the type of rheumatoid epitope were significant risk factors associated with relapse/recurrence. Cox proportional hazards modelling identified two variables that independently increased the risk of relapse/recurrence: ESR at diagnosis > 72 mm 1st h (RR=1.5) and type 2 (encoded by a non-DR4 allele) rheumatoid epitope (RR=2.7).
Conclusion:
These data from a Mediterranean country showed no association of rheumatoid epitope with PMR in northern Italian patients. A high ESR at diagnosis and the presence of rheumatoid epitope encoded by a non-DR4 allele are independent valuable markers of disease severity.
Insights
In polymyalgia rheumatica (PMR), HLA-DRB1 alleles showed no association. However, high erythrocyte sedimentation rate and specific rheumatoid epitopes independently predict disease relapse.
Area of Science:
- Immunogenetics
- Rheumatology
Background:
- Polymyalgia rheumatica (PMR) is an inflammatory condition.
- The role of Human Leukocyte Antigen (HLA) genes, particularly HLA-DRB1 alleles, in PMR pathogenesis and severity is not fully understood.
Purpose of the Study:
- To investigate the association between HLA-DRB1 alleles and PMR in a Mediterranean population.
- To explore the influence of HLA-DRB1 genes on PMR disease severity and relapse risk.
Main Methods:
- A prospective follow-up study involved 92 PMR patients, 29 rheumatoid arthritis (RA) patients, and 148 controls.
- HLA-DRB1 alleles were determined using polymerase chain reaction and oligonucleotide hybridization.
- Risk factors for relapse/recurrence were analyzed using univariate and Cox proportional hazards modeling.
Main Results:
- No significant differences in HLA-DRB1 types or shared epitope expression were found between PMR patients and controls.
- High erythrocyte sedimentation rate (ESR) at diagnosis (> 72 mm/1st h) and a type 2 rheumatoid epitope (non-DR4 allele) were significant independent predictors of relapse/recurrence.
Conclusions:
- In this Northern Italian cohort, HLA-DRB1 alleles and the shared epitope are not associated with PMR.
- Elevated ESR at diagnosis and a specific non-DR4 encoded rheumatoid epitope are valuable markers for predicting PMR disease severity and relapse.