Interleukin-23 Receptor Gene Polymorphism May Enhance Expression of the IL-23 Receptor, IL-17, TNF-α and IL-6 in Behcet’s Disease

<div><p>Purpose</p><p>Recent studies identified an association between Behcet’s disease (BD) and the IL-23R gene polymorphism (rs17375018) in different populations. This study examined whether this IL-23R gene polymorphism is associated with enhanced inflammatory responses.</p><p>Methods</p><p>We recruited 27 BD patients and 32 controls with three genotypes. Peripheral blood mononuclear cells (PBMCs) were seeded with or without anti-CD3 and CD28. Cells were incubated for 24 hours, and then supernatants were collected and stored at −20◦C until analyzed. Levels of interferon (IFN)-γ, tissue necrosis factor (TNF)-α, interleukin (IL)-17 and IL-6 were detected by ELISA. IL-23R expression was assessed by quantitative real-time polymerase chain reaction (RT-PCR).</p><p>Results</p><p>The expression of IL-23R was significantly higher in both BD patients and healthy controls with the GG genotype compared to the AG and AA genotype with anti-CD3 and CD28 stimulation (all P-value < 0.05). Among the PBMCs cultured with anti-CD3 and CD28 stimulation, there was an elevated secretion of TNF-α, IL-6 and IL-17 in BD patients and healthy controls with the GG genotype. However, there was no significant change in secretion of IFN- γ in BD patients and healthy controls among the genotype of this IL-23R gene polymorphism.</p><p>Conclusions</p><p>The results suggest that the GG genotype of the rs17375018 variant in the IL-23R gene enhances pro-inflammatory cytokine responses.</p></div

The IL-17, IFN-γ, TNF-α and IL-6 expression levels of peripheral blood mononuclear cells (PBMC) obtained from healthy individuals and patients with Behcet’s disease with the rs17375018 AA, AG and GG genotypes.

<p>The IL-17, IFN-γ, TNF-α and IL-6 expression levels of peripheral blood mononuclear cells (PBMC) obtained from healthy individuals and patients with Behcet’s disease with the rs17375018 AA, AG and GG genotypes.</p

Clinical characteristic of study participants.

<p>Clinical characteristic of study participants.</p

Clinical features of the investigated AS patients and controls.

<p>Clinical features of the investigated AS patients and controls.</p

Primers and restriction enzymes used for RFLP analysis of the IL23R gene.

<p>Primers and restriction enzymes used for RFLP analysis of the IL23R gene.</p

Frequencies of alleles and genotypes of <i>IL23R</i> polymorphisms in AS patients and controls.

<p>OR = odds ratio; 95% CI = 95% confidence interval; <i>p</i>c = Bonferroni corrected <i>P</i>; NS = not significant.</p

Frequencies of alleles and genotypes of <i>IL23R</i> polymorphism in <i>HLA-B27-</i>positive AS patients and controls.

<p>OR = odds ratio; 95% CI = 95% confidence interval;</p><p><i>p</i>_c = Bonferroni corrected <i>P</i>; NS = not significant.</p

Primers and restriction enzymes used for PCR-RFLP analysis.

<p>Primers and restriction enzymes used for PCR-RFLP analysis.</p

Genotype and allele frequencies of <i>PD-1</i>, <i>PD-L1</i> SNPs in Behcet's patients and healthy controls.

*<p>, <i>Pc</i> = 0.279 (n = 9).</p

Clinical features of the investigated patients with Behcet's disease.

<p>Abbreviations: SD, standardized deviation.</p