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* = Presenting author

P076 IL-26 genetic polymorphisms impair cytokine response to bacterial DNA translocation and increase anti-TNF consumption in patients with Crohn's disease

Piñero P.*1, Juanola O.1, Gutiérrez A.1, Zapater P.1, Giménez P.1, Steinert A.2, Sempere L.1, Gonzalez-Navajas J.M.1, Niess J.2, Francés R.1

1CIBERehd - Hospital General Universitario de Alicante, Alicante, Spain 2Basel University, Basel, Switzerland

Background

Interleukin (IL)-26 is secreted by IL-17-producing helper T cells to support killing of microbes and innate sensing of bacterial derived DNA (bactDNA). BactDNA translocation has been reported in patients with Crohn's disease (CD). We aimed at evaluating the relationship between IL-26 serum levels and bactDNA translocation in CD patients, as distributed by common IL-26 polymorphisms.

Methods

Prospective observational study on CD patients in remission, as established by CDAI<150. IL-26 rs1558744, rs7134599, and rs2870946 polymorphisms were genotyped. IL-26 levels and the concentration of amplified bactDNA in blood were measured. Serum TNF-alpha and free anti-TNF-alpha levels were evaluated according to IL-26 SNPs genotypes and bactDNA presence.

Results

313 patients were included (Mean CDAI: 83.6±32.8; Mean fecal calprotectin: 55.4±35.3μg/g). 106 patients showed bactDNA fragments in the blood (33.8%), which belonged to the Enterobacteriaceae family in 77% of cases. IL-26 SNP allelic frequencies were 53%, 12.3% and 46.5% for rs1558744 (A>G), rs7134599 (T>C), and rs2870946 (G>A), respectively. The rate of bactDNA translocation among patients distributed by the number of IL-26 SNPs was 34.4% (31/90) in patients without; 45.6% (26/57) in patients with one; 28.8% (36/125) in patients with two; and 31.7% (13/41) in patients with three IL-26 SNPs (p=ns). Serum IL-26 levels were significantly increased in patients with vs. without bactDNA in the blood (98.4±36.6 vs 16.6±10.2 pg/mL, p=0.01), and remained significantly higher irrespective of each studied SNP genotype. The accumulation of IL-26 SNPs was associated with a significant reduction in IL-26 serum levels among patients with bactDNA, although they remained higher than levels in patients without bactDNA in all cases, even in those with all three studied IL-26 SNPs. IL-26 SNPs significantly reduced TLR-9 mRNA expression in patients with bactDNA compared to those without the studied SNPs. The overall correlation found between TLR-9 mRNA expression levels and the amount of amplified bactDNA (r=0.67; p=0.01) was due to patients without or with one IL-26 SNP. Among patients on biologics, a significant reduction in serum TNF-α levels was only achieved in the absence of IL-26 SNPs. The presence of studied SNPs was associated with a reduced amount of free anti-TNF-α serum levels in patients with two or more IL-26 SNPs. An inverse correlation was present between free anti-TNF-α and IL-26 serum levels (r=−0.36; p=0.01).

Conclusion

IL-26 SNPs may compromise translocated bactDNA clearance in CD patients, facilitating an upheld proinflammatory environment. This may contribute to an increased anti-TNF-α consumption in CD patients with bactDNA.