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J Mol Med (Berl). 2017 Nov;95(11):1227-1236. doi: 10.1007/s00109-017-1585-6. Epub 2017 Sep 6.

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

Author information

1
CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
2
Instituto ISABIAL, Hospital General Universitario de Alicante, Alicante, Spain.
3
Departamento Medicina Clínica, Universidad Miguel Hernández, San Juan de, Alicante, Spain.
4
Servicio de Medicina Digestiva, Hospital General Universitario de Alicante, Alicante, Spain.
5
Servicio de Farmacología Clínica, Hospital General Universitario de Alicante, Alicante, Spain.
6
University Clinic of Visceral Surgery and Medicine, Inselspital Bern, Bern, Switzerland.
7
Departments of Biomedicine and Gastroenterology and Hepatology, Basel University, Switzerland Basel, Basel, Switzerland.
8
CIBERehd, Instituto de Salud Carlos III, Madrid, Spain. frances_rub@gva.es.
9
Instituto ISABIAL, Hospital General Universitario de Alicante, Alicante, Spain. frances_rub@gva.es.
10
Departamento Medicina Clínica, Universidad Miguel Hernández, San Juan de, Alicante, Spain. frances_rub@gva.es.

Abstract

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 may prevent bactDNA clearance and identify CD patients with a worse inflammatory evolution and response to therapy.

KEY MESSAGES:

BactDNA translocation in CD is associated with an increased risk of relapse. IL26 is sensitive to bactDNA and modulates the inflammatory response in CD patients. The varIL26 genotype is associated with reduced PMN capacity to kill bacteria. A varIL26 genotype is associated with decreased levels of anti-TNF-α in CD patients. IL26 may help explain the role of bactDNA as a risk factor of flare in CD patients.

KEYWORDS:

Bacterial translocation; Crohn’s disease; Interleukin 26

PMID:
28879509
DOI:
10.1007/s00109-017-1585-6
[Indexed for MEDLINE]

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