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FcγR expression on NK cells influences disease severity in rheumatoid arthritis

Genes & Immunity volume 5, pages 521–529 (2004)Cite this article

Abstract

Rheumatoid arthritis (RA) is associated with autoantibodies, the best known of which is rheumatoid factor (RF). RF/IgG complexes interact with FcγR on the surface of neutrophils, NK cells and monocyte/macrophages. We have analyzed the expression pattern and allelic polymorphisms of three FcγR genes (FcγRIIA, FcγRIIC and FcγRIIIA) in a large sample of RA patients and normal donors. We have found that the level of FcγR (CD16 and CD32) expression on NK cells is lower in RA patients than in normal individuals. Genotypic analysis demonstrated that the CD32 isoform expressed by the majority of RA patients was not the activating FcγRIIc1 isoform, commonly seen in normal individuals, but rather the inhibitory FcγRIIb isoform. The combination of the FcγRIIIA-176F allele with a lack of CD32 expression in NK cells appeared to be characteristic of RA subjects with aggressive disease. Since FcγRII and FcγRIIIA are predominantly expressed by NK cells, these data further suggest that FcγR-mediated activation of NK cells could be a disease-determining factor in RA patients.

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Acknowledgements

This work was supported by a grant awarded by the Simeon M Jones Jr and Katharine Reed Jones Fund of The Pittsburgh Foundation, and by NIH Grant AI42204. We would like to thank Dewayne Falkner and Jason Scull for technical assistance. We would also like to thank Drs Diana Metes and Russell Salter for critical reading of the manuscript.

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Authors and Affiliations

  1. Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    AM Stewart-Akers & PA Morel

  2. Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    A Cunningham, MC Wasko & PA Morel

  3. University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    PA Morel

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  1. AM Stewart-Akers
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Correspondence to PA Morel.

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Stewart-Akers, A., Cunningham, A., Wasko, M. et al. FcγR expression on NK cells influences disease severity in rheumatoid arthritis. Genes Immun 5, 521–529 (2004). https://doi.org/10.1038/sj.gene.6364121

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