IL26 modulates cytokine response and anti-TNF consumption in Crohn’s disease patients with bacterial DNA

Interleukin il26 supports killing of microbes and the innate sensing of bacterial-derived dna (bactdna). we evaluated the relationship between il26 serum levels and bactdna translocation in crohn’s disease (cd). we ran a prospective study on cd patients in remission. il26 common polymorphisms, serum cytokines and complement protein, amplified-bactdna, and anti-tnf-α were evaluated. in vitro pbmc analysis was performed. three hundred and thirteen patients were included (mean cdai: 83.6 ± 32.8; mean fecal calprotectin: 55.4 ± 35.3 μg/g). a total of 106 patients (33.8%) showed bactdna and 223 patients (71%) had a varil26 genotype. bactdna significantly correlated with increased il26 levels compared with bactdna-negative patients. pbmcs from varil26 patients significantly reduced e. coli killing capacity compared with wtil26-genotyped patients. the stimulation with a recombinant il26 protein reduced pro-inflammatory cytokines in response to e. coli in the varil26 cell supernatants. serum anti-tnf-α levels in varil26 vs wtil26-genotyped patients on biologics were significantly lower in the presence of bactdna. cells from varil26 vs wtil26-genotyped patients cultured with e. coli dna and infliximab showed a significant decrease in free anti-tnf-α concentration. a varil26 genotype was associated with the initiation of anti-tnf-α in cd patients during the 6-month follow-up. il26 polymorphisms prevent bactdna clearance and identify cd patients with a worse inflammatory evolution and response to therapy.