IL-23R rs11209026 polymorphism modulates IL-17A expression in patients with rheumatoid arthritis
IL-23R rs11209026 polymorphism modulates IL-17A expression in patients with rheumatoid arthritis
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DOI：
10.1038/gene.2011.80
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发表时间：
2012-04-01
影响因子：
5
通讯作者：
Hessian, P. A.
中科院分区：
文献类型：
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作者：
Hazlett, J.;Stamp, L. K.;Hessian, P. A.
白细胞介素 (IL)-17/IL-23 轴是类风湿性关节炎 (RA) 中重要的促炎通路。 IL-23 维持 CD4(+) T 辅助细胞 17 (Th-17) 细胞，而 IL-12 通过促进 Th-1 细胞分化来抑制 IL-17A 的产生。我们在 81 名 RA 患者中寻找白细胞介素 23 受体 (IL-23R)、IL-12 或 IL-21 基因内的多态性对血清细胞因子浓度影响的证据。使用基于微珠的多重测定法测量血清细胞因子。在高达 66% 的样本中检测到了靶向细胞因子。 48 名患者的亚组可检测到血清 IL-17A。在该亚组中，与具有次要等位基因的患者相比，IL-23R rs11209026主要等位基因纯合的患者的血清IL-17A浓度显着较高（394.51 +/- 529.72 pg ml(-1) vs 176.11 +/- 277.32 pg ml(-1)；P=0.017）。在 IL-12B rs3213337、IL-12Bpro rs17860508 和 IL-21 rs6822844 次要等位基因阳性患者与主要等位基因纯合性患者中，检查的任何细胞因子浓度均无显着差异。我们的结果表明 IL-23R Arg381Gln 替代可能影响血清 IL-17A 浓度。在具有 381Gln 等位基因的患者中，可能需要更高的 IL-23 浓度才能产生与具有 381Arg 等位基因的患者相似的 IL-17A 浓度。这表明具有次要等位基因的患者的 IL-23R 功能发生了改变，并需要进一步的功能研究。
The interleukin (IL)-17/IL-23 axis is an important pro-inflammatory pathway in rheumatoid arthritis (RA). IL-23 maintains CD4(+) T-helper 17 (Th-17) cells, whereas IL-12 negates IL-17A production by promoting Th-1-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.