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Dw subtypes of DR4 in rheumatoid arthritis: evidence for a preferential association with Dw4
Abstract:
We have determined the frequency of the DR4-associated Dw subtypes, defined by homozygous typing cells, in a group of rheumatoid arthritis (RA) patients on second-line drug therapy. The frequency of DR4 in these patients was 86%. Among Caucasians, the frequency of Dw4 in the DR4-positive patients was significantly increased (68%) as compared to DR4-positive normal individuals (46%; p less than 0.025). Dw4, as compared to the other DR4 subtypes tested, may also be associated with more severe disease as judged by indices of functional impairment and joint damage. In a small subgroup of non-Caucasian (black and Native American) patients, the Dw13 (DB3) subtype of DR4 was often seen, suggesting that RA may have different Dw associations in different ethnic groups.
Insights
The human leukocyte antigen (HLA) DR4 subtype Dw4 is more common in Caucasian rheumatoid arthritis (RA) patients, potentially indicating a link to disease severity. Different Dw subtypes may be associated with RA in diverse ethnic groups.
Area of Science:
- Immunogenetics
- Rheumatology
- Human Leukocyte Antigen (HLA) complex
Background:
- Rheumatoid arthritis (RA) is a chronic autoimmune disease.
- Specific human leukocyte antigen (HLA) subtypes, particularly those within the DR4 locus, have been implicated in RA susceptibility.
- Understanding the frequency of these subtypes is crucial for elucidating disease pathogenesis and potential ethnic variations.
Purpose of the Study:
- To determine the frequency of DR4-associated Dw subtypes in rheumatoid arthritis (RA) patients undergoing second-line drug therapy.
- To investigate potential associations between specific Dw subtypes and disease severity.
- To explore ethnic differences in Dw subtype associations with RA.
Main Methods:
- Homozygous typing cells were used to define Dw subtypes.
- Frequencies of DR4 and its subtypes (Dw4, Dw13) were analyzed in RA patients and compared to normal individuals.
- Disease severity was assessed using indices of functional impairment and joint damage.
Main Results:
- The frequency of HLA-DR4 was high (86%) in the studied RA patients.
- The Dw4 subtype was significantly more frequent in Caucasian RA patients (68%) compared to controls (46%).
- Dw4 may be associated with increased functional impairment and joint damage in RA patients.
- The Dw13 (DB3) subtype was frequently observed in non-Caucasian RA patients.
Conclusions:
- The HLA-DR4 subtype Dw4 is significantly associated with rheumatoid arthritis in Caucasian populations and may correlate with disease severity.
- RA may exhibit different HLA-Dw subtype associations across diverse ethnic groups, highlighting the need for ethnically stratified research.