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

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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.

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Acknowledgements

This work was supported by Asociación Española de Gastroenterología. J.H.N is supported by the Swiss National Foundation (SNSF 310030_146290).

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Authors and Affiliations

  1. CIBERehd, Instituto de Salud Carlos III, Madrid, Spain

    Paula Piñero, Oriol Juanola, Ana Gutiérrez, Pedro Zapater, Paula Giménez, José M. González-Navajas & Rubén Francés

  2. Instituto ISABIAL, Hospital General Universitario de Alicante, Alicante, Spain

    Paula Piñero, Oriol Juanola, Ana Gutiérrez, Pedro Zapater, Paula Giménez, Laura Sempere, José M. González-Navajas & Rubén Francés

  3. Departamento Medicina Clínica, Universidad Miguel Hernández, San Juan de, Alicante, Spain

    Oriol Juanola & Rubén Francés

  4. Servicio de Medicina Digestiva, Hospital General Universitario de Alicante, Alicante, Spain

    Ana Gutiérrez & Laura Sempere

  5. Servicio de Farmacología Clínica, Hospital General Universitario de Alicante, Alicante, Spain

    Pedro Zapater

  6. University Clinic of Visceral Surgery and Medicine, Inselspital Bern, Bern, Switzerland

    Anna Steinert & Jan H. Niess

  7. Departments of Biomedicine and Gastroenterology and Hepatology, Basel University, Switzerland Basel, Basel, Switzerland

    Anna Steinert & Jan H. Niess

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  1. Paula Piñero
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  2. Oriol Juanola
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  3. Ana Gutiérrez
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  7. Laura Sempere
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  9. Jan H. Niess
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  10. Rubén Francés
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Corresponding author

Correspondence to Rubén Francés.

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The Ethics Committee of Hospital General Universitario de Alicante approved the study protocol.

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The authors declare that they have no conflicts of interest.

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Paula Piñero and Oriol Juanola are first authors

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Piñero, P., Juanola, O., Gutiérrez, A. et al. IL26 modulates cytokine response and anti-TNF consumption in Crohn’s disease patients with bacterial DNA. J Mol Med 95, 1227–1236 (2017). https://doi.org/10.1007/s00109-017-1585-6

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  • DOI: https://doi.org/10.1007/s00109-017-1585-6

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