IFNΛ3/4 locus polymorphisms and IFNΛ3 circulating levels are associated with COPD severity and outcomes

Adrian Egli, Jyotshna Mandal, Desiree M. Schumann, Michael Roth, Brad Thomas, D. Lorne Tyrrell, Francesco Blasi, Kostantinos Kostikas, Wim Boersma, Branislava Milenkovic, Alicia Lacoma, Katharina Rentsch, Gernot G.U. Rohde, Renaud Louis, Joachim G. Aerts, Tobias Welte, Antoni Torres, Michael Tamm, Daiana Stolz

Research output: Contribution to journalArticle

Abstract

Background: Interferon lambdas (IFNLs) have important anti-viral/bacterial and immunomodulatory functions in the respiratory tract. How do IFNLs impact COPD and its exacerbations? Methods: Five hundred twenty eight patients were recruited in a prospective observational multicentre cohort (PROMISE) study. The genetic polymorphisms (rs8099917 and rs12979860) within the IFNL3/4 gene region and circulating levels of IFNL3 in COPD patients were determined and associated with disease activity and outcome during a median follow-up of 24 months. Results: The GG genotype significantly influenced severe exacerbation rate (42 vs. 23%; p = 0.032) and time to severe exacerbation (HR = 2.260; p = 0.012). Compared to the TT or TG genotypes, the GG genotype was associated with severe dyspnoea (modified medical research council score ≥ median 3; 22 vs 42%, p = 0.030). The CC genotype of the rs12979860 SNP was associated with a poorer prognosis (body mass index, airflow obstruction, dyspnea and exercise capacity index ≥ median 4; 46 vs. 36% TC vs. 20.5% TT; p = 0.031). Patients with stable COPD and at exacerbation had significantly lower circulating IFNL3 compared to healthy controls (p < 0.001 and p < 0.001, respectively). Circulating IFNL3 correlated to post-bronchodilator FEV1%predicted and the tissue maturation biomarker Pro-collagen 3. Conclusion: IFNL3/4 polymorphisms and circulating IFNL3 may be associated with disease activity and outcomes in COPD.

Original languageEnglish
Article number51
JournalBMC Pulmonary Medicine
Volume18
Issue number1
DOIs
Publication statusPublished - Mar 21 2018

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Keywords

  • Biomarker
  • Cohort
  • Interleukin 28B
  • Mortality
  • Single nucleotide polymorphisms

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Egli, A., Mandal, J., Schumann, D. M., Roth, M., Thomas, B., Lorne Tyrrell, D., Blasi, F., Kostikas, K., Boersma, W., Milenkovic, B., Lacoma, A., Rentsch, K., Rohde, G. G. U., Louis, R., Aerts, J. G., Welte, T., Torres, A., Tamm, M., & Stolz, D. (2018). IFNΛ3/4 locus polymorphisms and IFNΛ3 circulating levels are associated with COPD severity and outcomes. BMC Pulmonary Medicine, 18(1), [51]. https://doi.org/10.1186/s12890-018-0616-6