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Immunosusceptibility genes in rheumatoid arthritis
M A Sherritt1, B Tait, M Varney
1Neuroimmunology Laboratory, La Trobe University, Bundoora, Australia.
Human Immunology
|November 1, 1996
Summary
Genetic factors, including HLA DRB1 sequences and female gender, significantly increase rheumatoid arthritis (RA) risk. Interactions between these factors and other genes modulate RA predisposition.
Area of Science:
- Immunogenetics
- Rheumatology
- Human Genetics
Background:
- Rheumatoid arthritis (RA) has a known polygenic predisposition, particularly linked to specific Human Leukocyte Antigen (HLA) DRB1 sequences.
- Disease susceptibility sequences in HVR3 of HLA DRB1 are strongly associated with RA-predisposing DR4 and DR1 subtypes.
Purpose of the Study:
- To investigate the predisposing interactions between genes encoding HLA and immunoglobulin molecules in rheumatoid arthritis.
- To compare the genetic background of Australian RA patients with ethnically matched controls.
Main Methods:
- Serological identification of HLA-A, B, and DR phenotypes.
- DNA typing for HLA-DR, DQ alleles, and DR4 subtypes.
- Restriction fragment length polymorphism (RFLP) analysis for Gm allogenotypes and immunoglobulin switch region polymorphisms.
Main Results:
- Confirmed higher frequencies of HLA DR4 or DR1 (77% vs 47%) and HVR3 susceptibility sequences (76%) in RA patients.
- Observed increased frequencies of HLA-B27, HLA-DQB1*0302 (DQ8), and Gm allotype 1,2,3;23 in RA patients, with specific associations by gender and HLA type.
- No significant differences in immunoglobulin switch region gene polymorphisms were found between patients and controls.
Conclusions:
- Female gender and HVR3 of HLA DRB1 are major genetic risks for RA.
- These risks are modulated by interactions between gender, HLA class I and II alleles, and Gm allotype.
- Further research into these complex genetic interactions is warranted for understanding RA pathogenesis.