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IL-23R rs11209026 polymorphism modulates IL-17A expression in patients with rheumatoid arthritis

Genes & Immunity volume 13, pages 282–287 (2012)Cite this article

Abstract

The interleukin (IL)-17/IL-23 axis is an important pro-inflammatory pathway in rheumatoid arthritis (RA). IL-23 maintains CD4+ T-helper 17 (Th17) cells, whereas IL-12 negates IL-17A production by promoting Th1-cell differentiation. We sought evidence for any effect of polymorphisms within the interleukin-23 receptor (IL-23R), IL-12 or IL-21 genes on serum cytokine concentrations in 81 patients with RA. Serum cytokines were measured using bead-based multiplex assays. Targeted cytokines were detected in up to 66% of samples. A subgroup of 48 patients had detectable serum IL-17A. Within this subgroup, patients, homozygous for the IL-23R rs11209026 major allele had significantly higher serum IL-17A concentrations compared with patients with the minor allele (394.51±529.72 pg ml–1 vs 176.11±277.32 pg ml–1; P=0.017). There was no significant difference in any of the cytokine concentrations examined in patients positive for the minor allele vs homozygosity for the major allele of IL-12B rs3213337, IL-12Bpro rs17860508 and IL-21 rs6822844. Our results suggest the IL-23R Arg381Gln substitution may influence serum IL-17A concentrations. In patients with the 381Gln allele higher IL-23 concentrations may be needed to produce similar IL-17A concentrations to those in patients with the 381Arg allele. This suggests altered IL-23R function in patients with the minor allele and warrants further functional studies.

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Acknowledgements

We are grateful to Debra McNamara, Jan Ipenburg and Jill Drake (research nurses) for assistance in collection of patient samples and Marilyn Merriman for technical assistance. This work was supported by The Health Research Council of New Zealand; Arthritis New Zealand; Lottery Health New Zealand and The Faculty of Medicine, University of Otago.

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Authors and Affiliations

  1. Department of Physiology, Leukocyte Inflammation Research Laboratory, University of Otago, Dunedin, New Zealand

    J Hazlett & P A Hessian

  2. Department of Medicine, University of Otago, Christchurch, New Zealand

    L K Stamp

  3. Department of Biochemistry, University of Otago, Dunedin, New Zealand

    T Merriman

  4. Department of Medicine, University of Otago, Dunedin, New Zealand

    J Highton

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  1. J Hazlett
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Correspondence to L K Stamp.

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Hazlett, J., Stamp, L., Merriman, T. et al. IL-23R rs11209026 polymorphism modulates IL-17A expression in patients with rheumatoid arthritis. Genes Immun 13, 282–287 (2012). https://doi.org/10.1038/gene.2011.80

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