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A monoclonal anti-idiotype specific for human polyclonal IgM rheumatoid factor
1Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461.
Journal of Immunology (Baltimore, Md. : 1950)
|June 15, 1992
Summary
A new antibody, 4C9, identifies a specific marker on rheumatoid factor (RF) in rheumatoid arthritis (RA) patients. This marker is predominantly found in the joints, suggesting local production of RF in RA.
Area of Science:
- Immunology
- Rheumatology
- Autoimmunity
Background:
- Rheumatoid arthritis (RA) is characterized by high levels of rheumatoid factor (RF), an antibody targeting IgG.
- Existing anti-idiotypic antibodies identify only a small fraction of RF from RA patients.
- Monoclonal RF from B cell malignancies differ from polyclonal RF in RA patients.
Purpose of the Study:
- To identify and characterize a novel monoclonal anti-idiotypic antibody, 4C9.
- To investigate the reactivity of 4C9 with rheumatoid factor (RF) from rheumatoid arthritis (RA) patients.
- To explore the potential site of synthesis for 4C9-reactive RF.
Main Methods:
- Development of a new monoclonal anti-idiotypic antibody, designated 4C9.
- Testing 4C9 reactivity against serum and synovial fluid samples from RA patients and controls.
- Analysis of purified IgM RF and IgG RF from RA patients.
Main Results:
- 4C9 recognizes a light chain determinant on polyclonal IgM RF in RA patients.
- 4C9 is reactive in a significant proportion of RF-positive RA sera (34/43) and synovial fluids (12/12).
- Reactivity is enriched in synovial fluid compared to serum, suggesting intra-articular synthesis of 4C9-reactive IgM RF.
Conclusions:
- 4C9 defines a unique idiotype on a subset of IgM RF in RA.
- The findings suggest that 4C9-reactive IgM RF are preferentially synthesized within the joint in RA patients.
- The lack of 4C9 reactivity on IgG RF implies distinct genetic or mutational pathways for IgM and IgG RF in RA.