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Identification of Clinically and Pathophysiologically Relevant Rheumatoid Factor Epitopes by Engineered IgG Targets
Willem J J Falkenburg1, Nienke Oskam2, Jana Koers2
1Amsterdam Rheumatology and Immunology Center, Reade, Sanquin Research, and Academic Medical Center, Amsterdam, The Netherlands.
Arthritis & Rheumatology (Hoboken, N.J.)
|July 11, 2020
Summary
This study introduces a new method to analyze rheumatoid factor (RF) binding patterns in IgG. These patterns can help predict arthritis development and differentiate between rheumatoid arthritis (RA) and Sjögren
Area of Science:
- Immunology
- Autoimmunity
- Rheumatology
Background:
- Rheumatoid factors (RFs) are autoantibodies against IgG, associated with rheumatoid arthritis (RA) but also present in other conditions.
- RFs target various epitopes on the IgG constant (Fc) domain, suggesting potential for disease-specific binding patterns.
- Current understanding of RF epitope specificity and its clinical implications requires further investigation.
Purpose of the Study:
- To develop and apply a novel approach for dissecting RF epitope binding patterns across different diseases.
- To investigate the association between specific RF binding patterns and clinical features like arthritis development and autoantibody status.
- To explore the potential of RF reactivity patterns in differentiating between RA and primary Sjögren's syndrome (SS).
Main Methods:
- Utilized bioengineered, natively folded IgG-Fc targets for analyzing RF reactivity.
- Serum samples from patients with seropositive arthralgia, RA, and primary SS were analyzed.
- Assessed selective RF binding toward distinct regions of the IgG-Fc domain, including the Elbow and Tail regions.
Main Results:
- RFs predominantly bound the Fc Elbow region, with some binding to the Fc Tail region; the Fc receptor binding site was rarely targeted.
- Restricted Fc Tail region reactivity correlated with lower anti-citrullinated protein antibody (ACPA) positivity and reduced arthritis development in arthralgia.
- Combined Fc Tail and Elbow region reactivity was associated with increased arthritis development, and Fc Tail reactivity was more frequent in RA than in primary SS.
Conclusions:
- Bioengineered IgG targets facilitate serologic characterization of RF reactivity, revealing patterns linked to ACPA status and arthritis development.
- Distinct RF binding patterns can differentiate RA patients from primary SS patients.
- This methodology enhances the clinical utility of RFs and deepens the understanding of their pathophysiological roles.
