IL-17 Phenotype May Represent Targeted Asthma Treatment Pathway

The presence of interleukin (IL)-17 asthma phenotypes can be “identified reliably” in patients with asthma, suggesting this biomarker should be further studied to develop targeted treatment options, according to a study published in the Journal of Allergy and Clinical Immunology.

Researchers with the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED; ClinicalTrials.gov Identifier: NCT01982162) study sought to further the understanding of both clinical features and molecular mechanisms of asthma, as characterized by upregulation of IL-17.

Study participants from the U-BIOPRED cohort (91 patients with asthma and 46 healthy controls) underwent spirometry, exhaled nitric oxide measurements (FeNO), sputum induction, and atopy assessment; whole blood samples were also collected, and bronchial brushings and biopsies were performed in the patients with asthma. The researchers analyzed the biopsies, brushings, and whole blood samples for whole genome expression, and then analyzed the data using liner model statistical tests and hierarchal clustering.

In total, the investigators collected 85 brushings and 68 biopsies from the 91 participants with asthma. Ten patients had an IL-13-high phenotype, 22 patients with asthma had an IL-17-high phenotype, and 60 patients had neither gene signature. These participants were defined as IL-13/IL-17-low phenotype.

Of the patients in the IL-17-high group, 59% had severe asthma, and 38% had >2 asthma exacerbations in the previous year. These patients also had an increased occurrence of nasal polyps (43%), a history of regular antibiotic use (27%), and a more significant smoking history.

The researchers noted that in their pathway analysis, they found that psoriasis was the disease with “the greatest overlap and significance,” but because the U-BIOPRED questionnaire did not ask about past or present psoriasis diagnoses, conclusions about disease comorbidity could not be drawn.

Study limitations included the limited availability of sputum samples from the IL-13-high phenotype and the “limited analysis of the microbiome,” in addition to the observational nature of the study.

“[W]e show that the IL-17 phenotype can be identified reliably, with clinical and immunological features that define a distinct disease phenotype,” the researchers concluded. “[W]e propose that there is a sufficient case for developing drugs for this phenotype.”

Disclosures: Multiple study authors reported relevant conflicts of interest. For a complete list of disclosures, please see the full text of the study online.

Reference

Östling J, van Geest M, Schofield JPR, et al; on behalf of the U-BIOPRED Study Group. IL-17-high asthma with features of a psoriasis immunophenotype [published online April 15, 2019]. J Allergy Clin Immunol. doi:10.1016/j.jaci.2019.03.027