Engineered IgG-targets identify clinically and pathophysiologically relevant rheumatoid factor epitopes

Falkenburg, W. J. J., Oskam, N., Koers, J., van Boheemen, L., Ooijevaar-de Heer, P., Verstappen, G. M., Bootsma, H., Kroese, F. G. M., van Schaardenburg, D., Wolbink, G. & Rispens, T., 10-Jul-2020, In : Arthritis & Rheumatology. 22 p.

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  • Engineered IgG‐targets identify clinically and pathophysiologically relevant rheumatoid factor epitopes

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OBJECTIVES: Rheumatoid factors (RFs), anti-IgG autoantibodies strongly associated with rheumatoid arthritis (RA), are also found in other diseases and in healthy individuals. RFs bind to various epitopes in the constant (Fc-) domain of IgG; therefore, disease-specific reactivity patterns may exist. A new approach was developed to dissect RF epitope binding patterns across different diseases.

METHODS: We analyzed RF reactivity patterns in patients with seropositive arthralgia, RA and primary Sjögren's syndrome (pSS), using bio-engineered, natively folded IgG-Fc targets featuring selective RF binding towards several distinct regions of IgG-Fc.

RESULTS: RF responses primarily bound the Fc elbow region, with a smaller contribution from the Fc tail region, while the Fc receptor-binding region was hardly targeted. A restricted reactivity against the IgG-Fc tail region was associated with less positivity for anti-citrullinated protein antibodies (ACPAs) and less arthritis development in arthralgia, whereas combined reactivity towards IgG-Fc tail and elbow regions associated with more arthritis development. Reactivity towards the IgG-Fc tail region was found far more frequently in RA than in pSS.

CONCLUSIONS: Bio-engineered IgG targets enable serological characterization of RF reactivity patterns and reveal patterns associated with ACPA detection and arthritis development in arthralgia patients. They separate RA patients from pSS patients. This new methodology improves the clinical value and our pathophysiological understanding of RFs.

Original languageEnglish
Number of pages22
JournalArthritis & Rheumatology
Publication statusE-pub ahead of print - 10-Jul-2020

ID: 135920475