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Regulation of rheumatoid factor synthesis
D A Carson1, P P Chen, T J Kipps
1Research Institute of the Scripps Clinic, La Jolla, California 92037.
Clinical and Experimental Rheumatology
|September 1, 1989
Summary
Rheumatoid factors (RF) are autoantibodies linked to rheumatoid arthritis. This study explores the genetic basis of RF production, suggesting Epstein-Barr virus may trigger self-reactive T cells, leading to RF synthesis.
Area of Science:
- Immunology
- Molecular Genetics
- Rheumatology
Background:
- Rheumatoid arthritis (RA) features high autoantibodies against IgG (rheumatoid factors, RF).
- Specific HLA haplotypes (Dw4, Dw14, DR1) are prevalent in RA patients.
- Understanding RF autoantibody synthesis is key to RA pathogenesis.
Purpose of the Study:
- To determine the molecular genetic basis of RF autoantibody synthesis.
- To investigate the regulation of RF production in rheumatoid patients.
- To identify potential triggers for aberrant RF synthesis.
Main Methods:
- Analysis of cross-reactive idiotypes on RF heavy and light chains.
- Investigation of immunoglobulin variable region gene expression.
- Examination of B cell subpopulations and antigen presentation.
- Study of T cell proliferation in response to viral proteins.
Main Results:
- Defined cross-reactive idiotypes as serologic markers for specific immunoglobulin genes.
- Identified RF-associated genes in early B cell development and lymphoproliferative diseases.
- Found RF-associated idiotypes are lost during RA antibody diversification.
- Demonstrated Epstein-Barr virus gp110 protein mimics RA susceptibility determinants and stimulates T cells.
Conclusions:
- RF precursor B cells may process viral antigen-IgG complexes, leading to self-reactive T cells.
- This process could trigger anti-IgG autoantibody synthesis in RA.
- Epstein-Barr virus is a potential environmental trigger for RA pathogenesis.