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Seronegative rheumatoid arthritis in elderly and polymyalgia rheumatica have similar patterns of HLA association
M A Gonzalez-Gay1, A H Hajeer, A Dababneh
1Hospital Xeral-Calde, Lugo, Spain.
Objective:
To examine whether polymyalgia rheumatica (PMR) and late onset rheumatoid arthritis have identical or similar HLA-DRB1 genetic associations.
Methods:
Seventy five PMR cases without evidence of giant cell arteritis were available for study. One hundred seven RA cases were investigated, of which 62 had disease onset after age 60 years. All cases were compared with 145 ethnically matched controls. All cases and controls originated from Lugo, NW Spain. HLA-DRB1 typing was performed on DNA samples using PCR based molecular methods.
Results:
Early onset RA (< or =40 yrs) was strongly associated with DRB1*04 (DRB1*0401 and *0404). In contrast late onset RA (> or = 60 yrs) was not associated with DRB1*04 but was associated with DRB1*01. Stratification of late onset RA cases by rheumatoid factor status revealed that DRB1*01 was only increased in seropositive RA cases. Late onset seronegative RA cases exhibited increased frequency of DRB1*13/*14; this was also observed in PMR cases where coexistence of GCA had been excluded.
Conclusion:
These data indicate that (1) HLA associations with RA differ with respect to age at disease onset; and (2) seronegative late onset RA and "isolated" PMR have a similar HLA-DRB1 association and may have an identical etiological basis.
Insights
Polymyalgia rheumatica (PMR) and late-onset rheumatoid arthritis (RA) share similar HLA-DRB1 genetic associations, particularly in seronegative cases. This suggests a potential common etiological basis for these distinct conditions.
Area of Science:
- Rheumatology
- Immunogenetics
- Human Leukocyte Antigen (HLA) complex
Background:
- Rheumatoid arthritis (RA) and polymyalgia rheumatica (PMR) are inflammatory conditions affecting older adults.
- Genetic factors, particularly Human Leukocyte Antigen (HLA) alleles, are implicated in the pathogenesis of RA.
- The specific HLA-DRB1 associations in PMR and late-onset RA (LORA) require further elucidation.
Purpose of the Study:
- To investigate and compare the Human Leukocyte Antigen-DRB1 (HLA-DRB1) genetic associations in polymyalgia rheumatica (PMR) and late-onset rheumatoid arthritis (LORA).
- To determine if PMR and LORA share similar or identical genetic predispositions.
- To explore the influence of rheumatoid factor status on HLA-DRB1 associations in LORA.
Main Methods:
- A cohort of 75 PMR cases (excluding giant cell arteritis) and 107 RA cases (62 with late onset) were studied.
- Cases were compared with 145 ethnically matched controls from Lugo, NW Spain.
- HLA-DRB1 typing was performed using Polymerase Chain Reaction (PCR) based molecular methods on DNA samples.
Main Results:
- Early-onset RA (< or =40 yrs) showed a strong association with HLA-DRB1*04 alleles.
- Late-onset RA (> or =60 yrs) was not associated with HLA-DRB1*04 but was linked to HLA-DRB1*01, particularly in seropositive cases.
- Late-onset seronegative RA and PMR (GCA excluded) exhibited a similar increased frequency of HLA-DRB1*13/*14 alleles.
Conclusions:
- HLA-DRB1 associations with rheumatoid arthritis vary significantly based on age of disease onset.
- Seronegative late-onset RA and PMR (without giant cell arteritis) share a common HLA-DRB1 association profile.
- The shared genetic associations suggest a potential identical etiological basis for seronegative LORA and isolated PMR.
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