AATD-AT, but not AATD-noT patients, had IL-27 sputum levels (pg/ml) significantly lower than COPD (<i>p</i>=0.0297) and these positively correlated with FEV<sub>1</sub>% predicted values (<i>r</i>=0.578, <i>p</i>=0.0307).
Disease type-stratified subgroup analysis yielded increased risk of related diseases in IL-27rs181206 T>C carriers in the allele model in immune thrombocytopenia (ITP), asthma, and esophageal cancer (EC) subgroups (ITP: OR=0.69, 95%CI=0.53~0.88, P=0.004; asthma: OR=0.60, 95%CI=0.41~0.89, P=0.010; EC: OR=0.79, 95%CI=0.64~0.97, P=0.026); and IL-27rs153109 A>G polymorphism was remarkably associated with the increased risk of related diseases in the allele model in ovarian cancer (OC), systemic lupus erythematosus (SLE), tuberculosis (TB), ulcerative colitis (UC), and chronic obstructive pulmonary disease (COPD) subgroups (all P<0.05).
In an exome array analysis of COPD, we identified nonsynonymous variants at previously described loci and a novel exome-wide significant variant in IL27.
We identify a novel tolerogenic circuit encompassing suppressive CD1c(+) DCs and regulatory T cells in patients with COPD that might be implicated in impaired respiratory immunity and further highlight IL-10 and IL-27 as potent therapeutic targets.
Finally, clinical analysis showed that IL-27 was detected in the bronchoalveolar lavage of patients with asthma, chronic obstructive pulmonary disease (COPD), and pulmonary tuberculosis (PTB), and increased IL-27 concentrations were correlated with increased CXCL10 concentrations in patients with COPD and PTB.
When compared with the control group, subjects with AG genotype of the IL-27-964A/G had a 2.22-fold decreased risk of COPD (odds ratio [OR] = 0.450, 95% confidence interval [CI]: 0.245-0.826; p = 0.009), and subjects with TG genotype of the IL-272905T/G had a 2.85-fold decreased risk of COPD (OR = 0.351, 95% CI: 0.137-0.899; p = 0.024).
Even after Bonferroni corrections, significant associations with COPD were observed for the AG genotype of the IL-27 -964A/G and the TGG haplotype of the IL-27 gene.