Sputum cell IL-1 receptor expression level is a marker of airway neutrophilia and airflow obstruction in asthmatic patients

Michael D. Evans, Stephane Esnault, Loren C. Denlinger, Nizar N. Jarjour

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Background: Various clinical, biologic, or physiologic markers of asthma have been used to identify patient clusters and potential targets for therapy. However, these identifiers frequently overlap among the different asthma groups. For instance, both eosinophil and neutrophil counts are often increased in the airways of asthmatic patients despite their typical association with type 2 and type 17 immune response, respectively. Objectives: We sought to determine whether inflammatory gene expression is related to patterns of airway inflammation and lung function and identify molecular markers for neutrophilic asthma. Methods: Expression levels of 17 genes characterizing type 1, type 2, and type 17 lymphocytes were measured in sputum samples from 48 participants with asthma. The relationships between gene expression levels and sputum cell differentials or measures of pulmonary function were examined by using partial least squares regression. Results: Gene expression levels were strongly associated with cell differentials, explaining 71% of variation in eosinophil counts and 64% of variation in neutrophil counts. The 3 genes with the strongest relationships to sputum neutrophil counts were IL1R1 (standardized regression coefficient [β] = +0.27, P =.005), IL1RAP (β = +0.32, P =.0004), and IL4R (β = +0.29, P =.002). Higher expression levels of IL1R1, IL1RAP, and IL4R were associated with reduced FEV1/forced vital capacity ratio (β = −0.11, −0.08, and −0.10; P =.005,.07, and.05). Conclusion: IL-1 receptor appears to be a marker of neutrophilic inflammation and airflow obstruction in patients with asthma, who have a wide range of disease severity. The IL-1 pathway might contribute to airway neutrophilia and is a potential therapeutic target in patients with neutrophilic asthma.

Original languageEnglish (US)
Pages (from-to)415-423
Number of pages9
JournalJournal of Allergy and Clinical Immunology
Volume142
Issue number2
DOIs
StatePublished - Aug 2018
Externally publishedYes

Bibliographical note

Funding Information:
Disclosure of potential conflict of interest: M. D. Evans has received a grant from the National Institutes of Health. L. C. Denlinger reports grants from the National Heart, Lung, and Blood Institute (NHLBI) and personal fees from GlaxoSmithKline and Sanofi. N. N. Jarjour has received a grant from the NHLBI. S. Esnault declares that she has no relevant conflicts of interest.

Funding Information:
Supported by the Severe Asthma Research Program grants R01 HL069116 and U10 HL109168, Program Project grant P01 HL088594, and Clinical and Translational Research Center grants UL1 RR025011 and UL1 TR000427 from the National Institutes of Health.

Publisher Copyright:
© 2017 American Academy of Allergy, Asthma & Immunology

Keywords

  • Asthma
  • IL-1 receptor
  • lymphocyte
  • neutrophil
  • partial least squares
  • pulmonary function
  • sputum samples
  • type 1
  • type 17
  • type 2

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