Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 129, Issue 1, Pages 169-181Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI121087
Keywords
-
Categories
Funding
- NIH [U19AI077439, K23HL123778, K12HL11999, K24HL137013, R01HL121774, U01 HL137880]
- RESPIRE2 grant from the European Respiratory Society
- UCSF Cystic Fibrosis Cell Models Core (NIH) [DK072517]
- UCSF Cystic Fibrosis Cell Models Core (Cystic Fibrosis Foundation) [DR613-CR11]
- Netherlands Organization for Scientific Research (NWO)
- Dutch Asthma Foundation
- GlaxoSmithKline
- University Medical Center Groningen
- Leiden University Medical Center
- NIH/National Heart, Lung, and Blood Institute [HHSN268200900013C, HHSN268200900014C, HHSN268200900015C, HHSN268200900016C, HHSN268-200900017C, HHSN268200900018C, HHSN268200900019C, HHSN268200900020C]
- Foundation for the NIH
- COPD Foundation by AstmZeneca/MedImmune
- Bayer
- Bellerophon Therapeutics
- Boehringer-Ingelheim Pharmaceuticals Inc.
- Chiesi Farmaceutici SpA
- Forest Research Institute Inc.
- Grifols Therapeutics Inc.
- Ikaria Inc.
- Nycomed GmbH
- Takeda Pharmaceutical Co.
- Novartis Pharmaceuticals Corp.
- ProterixBio
- Regeneron Pharmaceuticals Inc.
- Sanofi
- Sunovion
Ask authors/readers for more resources
BACKGROUND. Chronic obstructive pulmonary disease (COPD) is a heterogeneous smoking-related disease characterized by airway obstruction and inflammation. This inflammation may persist even after smoking cessation and responds variably to corticosteroids. Personalizing treatment to biologically similar molecular phenotypes may improve therapeutic efficacy in a COPD. IL-17A is involved in neutrophilic inflammation and corticosteroid resistance, and thus may be particularly important in a COPD molecular phenotype. METHODS. We generated a gene expression signature of IL-17A response in bronchial airway epithelial brushings from smokers with and without COPD (n = 238) , and validated it using data from 2 randomized trials of IL-17 blockade in psoriasis. This IL-17 signature was related to clinical and pathologic characteristics in 2 additional human studies of COPD: (a) SPIROMICS (n = 47), which included former and current smokers with COPD, and (b) GLUCOLD (n = 79), in which COPD participants were randomized to placebo or corticosteroids. RESULTS. The IL-17 signature was associated with an inflammatory profile characteristic of an IL-17 response, including increased airway neutrophils and macrophages. In SPIROMICS the signature was associated with increased airway obstruction and functional small airways disease on quantitative chest CT. In GLUCOLD the signature was associated with decreased response to corticosteroids, irrespective of airway eosinophilic or type 2 inflammation. CONCLUSION. These data suggest that a gene signature of IL-17 airway epithelial response distinguishes a biologically, radiographically, and clinically distinct COPD subgroup that may benefit from personalized therapy.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available