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The presence of FCGR2B promoter or transmembrane region variant alleles leads to reduced serum IL-6 levels in rheumatoid arthritis

  • Original Article - Genes and Disease
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Abstract

The inhibitory FcγRIIB plays an important role for the peripheral B cell tolerance and plasma cell homeostasis, and any malfunctioning is predicted to result in humoral autoimmunity. An association between rheumatoid arthritis (RA) and FCGR2B promoter and TM region variant alleles, both of which result in a reduced functionality, is only insufficiently elucidated. We here set out to investigate the impact of these variants on disease progression in European RA patients. One hundred and five ACPA-positive RA patients were genotyped for the FCGR2B -386G>C promoter and the 695T>C transmembrane region variants. Moreover, serum titers for IL-6, TNFα, CTX-1 and ACPAs were measured and peripheral blood T cell and B cell populations analyzed for expression of the activation markers CTLA-4 and CD86. The presence of an FCGR2B variant allele results in reduced serum IL-6, a trend toward later disease onset and reduced requirement for biological treatment, but does not seem to aggravate RA. Likewise, the presence of the TM region variant allele is associated with a lower activation state of the Tregs and of naïve and memory B cells. The observation of a malfunctioning FcγRIIb not aggravating RA is counterintuitive at first. However, the etiology of RA is linked to inflammatory episodes, and the lack of B cell inhibition may support an accelerated antibody-mediated clearance of the disease initiating and perpetuating agents. It would thereby shorten inflammatory episodes, postpone the onset of disease and result in a less severe course of RA in carriers of FCGR2B variant alleles.

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Acknowledgments

We thank Birgit Ahrens for collecting the patients’ data and Ni Wang for help with the flow cytometry. This work was supported by an intramural fund (FORUN) and a research grant from Pfizer.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Institute of Immunology, University Medicine Rostock, Schillingallee 69, 18057, Rostock, Germany

    Stefanie Meister, Robby Engelmann & Brigitte Müller-Hilke

  2. Hospital Südstadt Rostock, Südring 81, 18059, Rostock, Germany

    Christian Kneitz

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  1. Stefanie Meister
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  2. Robby Engelmann
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  3. Christian Kneitz
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  4. Brigitte Müller-Hilke
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Correspondence to Brigitte Müller-Hilke.

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Meister, S., Engelmann, R., Kneitz, C. et al. The presence of FCGR2B promoter or transmembrane region variant alleles leads to reduced serum IL-6 levels in rheumatoid arthritis. Rheumatol Int 35, 1311–1318 (2015). https://doi.org/10.1007/s00296-015-3226-0

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  • DOI: https://doi.org/10.1007/s00296-015-3226-0

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