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

[en] 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. © 2018 The Author(s).

Disciplines :

Cardiovascular & respiratory systems

Author, co-author :

Egli, Adrian; University of Basel, Applied Microbiology Research, Department of Medicine, Basel, Switzerland, University Hospital Basel, Clinical Microbiology, Basel, Switzerland

Mandal, Jyotshna; University Hospital Basel, Clinic of Pneumology and Pulmonary Cell Research, Petersgraben 4, Basel, Switzerland

Schumann, Desiree M.; University Hospital Basel, Clinic of Pneumology and Pulmonary Cell Research, Petersgraben 4, Basel, Switzerland

Roth, Michael; University Hospital Basel, Clinic of Pneumology and Pulmonary Cell Research, Petersgraben 4, Basel, Switzerland

Thomas, Brad S.; University of Alberta, Li Ka Shing Institute for Virology, Edmonton, Canada

Lorne Tyrrell, D.; University of Alberta, Li Ka Shing Institute for Virology, Edmonton, Canada

Blasi, Francesco B.; Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milan, Italy

Kostikas, Konstantinos T.; University Hospital Basel, Clinic of Pneumology and Pulmonary Cell Research, Petersgraben 4, Basel, Switzerland

Boersma, Willem Germen; Department of Pneumology, Medisch Centrum Alkmaar, Alkmaar, Netherlands

Milenkovic, Branislava A.; Department of Pneumology, Institute for Pulmonary Diseases, Belgrade, Serbia

More authors (9 more)

Language :

English

Title :

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

Publication date :

21 March 2018

Journal title :

BMC Pulmonary Medicine

eISSN :

1471-2466

Publisher :

BioMed Central Ltd.

Volume :

Issue :

Pages :

Peer reviewed :

Peer Reviewed verified by ORBi

Name of the research project :

SNSF PP00P3_128412/1); University of Basel “Nachwuchsförderung”; SNSF Ambizione, PZ00P3_154709/1

Funders :

SNSF - Swiss National Science Foundation
UNIBAS - Universität Basel

Available on ORBi :

since 12 October 2019

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