Background
IL23 receptor (IL23R) binding by IL23 is required for the maturation of CD4
+
cells into Th17 cells and subsequent generation of IL17A and TNF. As IL23R variations contribute to AS susceptibility, we investigated the effect of
IL23R
variants on cytokine levels and disease measures in an AS cohort.
Methods
This was a cross-sectional study of AS patients (
n
= 334, 90% B27
+
, age 45 years).
IL23R
genotyping for three non-synonymous single-nucleotide polymorphisms (rs11209026, protective allele A; rs10489629, protective allele A; and rs11209032, risk allele A) was done by Taqman RT-PCR. IL23, IL17A, TNF and IL6 concentrations were determined by sandwich ELISA. Genotypic associations were analysed with non-parametric methods.
Results
Twenty-two AS patients (6.6%) carried the protective rs11209026 A allele, whereas 206 (61.7%) carried the rs11209032A risk allele (
P
= 0.03). Two patients homozygous for rs11209026A had late onset, no co-morbidity and undetectable cytokine levels.
IL23R
genotypes and five common haplotypes were unrelated with age at onset, BASFI or co-morbidity (all
P
>0.2). There was no overall difference in the concentration of IL17A (184
vs
233 pg/ml,
P
> 0.2) or IL23 (276
vs
262 pg/ml,
P
> 0.4) between AS patients and controls, but a global haplotype association (
P
= 0.01) was observed for IL23 concentrations.
Conclusion
Homozygosity for rs11209026A is rare in AS patients, but may ameliorate the clinical presentation. IL17A and IL23 levels are similar in controls and AS patients.
IL23R
variants influence IL23 levels but not IL17A levels in AS patients, suggesting that IL23R impacts more on cell types other than Th17 cells.