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Antigen binding differences between secreted and cell surface expressed rheumatoid factor derived from inflamed
T P Kenny1, P Leider, P A Duong
1Department of Internal Medicine, School of Medicine, University of California, Davis 95616, USA.
The Journal of Rheumatology
|May 1, 1996
Summary
Surface rheumatoid factor (RF) on B cells may bind differently than secreted RF, potentially impacting rheumatoid arthritis (RA) pathogenesis. This study explored these distinct binding specificities using novel assays.
Area of Science:
- Immunology
- Rheumatology
- Autoimmunity
Background:
- Rheumatoid factor (RF) is a key autoantibody in rheumatoid arthritis (RA).
- The precise role of RF in RA pathogenesis remains incompletely understood.
- Distinct binding properties of surface-bound RF (sRF) versus secreted RF are hypothesized.
Purpose of the Study:
- To investigate the differential binding specificities of sRF compared to secreted RF.
- To explore the potential pathogenic implications of these binding differences in RA.
- To differentiate RF binding characteristics based on its physical state (surface-bound vs. secreted).
Main Methods:
- Development and utilization of a novel RF antigen capture enzyme-linked immunoassay (ACE) to mimic sRF binding.
- Comparison of RF binding using ACE with a direct binding enzyme-linked immunoassay (DBE) that mimics secreted RF.
- Analysis of rheumatoid synovial cell (RSC)-derived monoclonal RF (mRF) binding patterns.
Main Results:
- Significant variations in binding characteristics were observed between ACE and DBE for the same mRF.
- Certain mRF exhibited altered IgG subclass binding (e.g., binding to IgG3 in ACE when only IgG1, 2, and 4 were bound in DBE).
- Some mRF demonstrated cross-species reactivity differences (binding human IgG in ACE vs. only rabbit IgG in DBE).
Conclusions:
- Differences in RF reactivity suggest conformational changes in RF and IgG molecules.
- Altered binding sites or exposed epitopes may depend on the antibody and antigen's physical state.
- These reactivity differences may hold significant pathogenic importance in rheumatoid arthritis.