Identification of Serum Biomarkers for CD15+ Hypodense Neutrophils in Severe Asthma

The goal of this study is to identify a serum biomarker(s) that can detect increased levels of a population of CD15+ hypodense neutrophils termed low-density granulocytes (LDG) in the blood of patients with severe persistent asthma.

Study Overview

• Status: Completed
• Conditions: Severe Persistent Asthma

Detailed Description

Neutrophils are implicated in the pathophysiology of multiple asthma phenotypes. It was shown in study IST Q4935s that low-density granulocytes (LDG) are elevated in the blood of patients with moderate or severe asthma. The greatest frequency and the highest percentages of LDG were observed in subjects with severe asthma. The LDG, which were first identified and characterized in systemic lupus erythematosus (SLE) patients, have been reported to display increased cytotoxicity for endothelial cells, increased tendency to form neutrophil extracellular traps, and increased production of tumor necrosis factor (TNF). It was also observed that the LDG expressed increased levels of CD15, which can facilitate attachment of activated platelets to the LDG. Identification of a putative serum biomarker that correlates with increased levels of the CD15+ LDG may be useful for the detection of neutrophil-associated inflammation in severe asthma.

Thirty subjects will be screened to identify 20 subjects with severe persistent asthma. The following data and/or samples will then be obtained within three weeks of the clinical assessment: (1) the percentages of LDG will be quantified by flow cytometry; (2) a blood sample will be collected into a PAXgene Blood tube and stored until shipped to Genentech for gene profiling analysis; and (3) a serum sample will be collected for measurement of total immunoglobulin E (IgE) and for future confirmation of potential biomarkers identified in the gene profiling analyses.

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University Consultants in Allergy/Immunology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Thirty prospective subjects will be screened to identify 20 subjects with severe persistent asthma. These subjects will be recruited from the Allergy/Immunology outpatient clinic at Rush University Medical Center along with self-referral through advertising posted on campus.

Description

Inclusion Criteria:

• Physician diagnosis of severe persistent asthma;
• Positive skin test or radioallergosorbent test (RAST) for an aeroallergen;
• Male or female age 12-65 years;
• Non-smoker.

Exclusion Criteria:

• Asthma exacerbation requiring treatment with or increase in oral corticosteroids within 30 days prior to the study;
• Respiratory infection within 30 days prior to the study;
• Starting or requiring a change in allergen immunotherapy within 30 days prior to the study;
• Having been treated with Xolair within the past year;
• Requiring chronic immunosuppressive therapy;
• Having taken methotrexate, gold salts, cyclosporine, or macrolide antibiotics within 3 months prior to study;
• Having taken an investigational drug within 30 days prior to the study;
• Have a history of drug or alcohol abuse;
• Pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Severe Persistent Asthma; All subjects will have severe persistent asthma diagnosed by a doctor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of low density granulocytes (LDG) in the peripheral blood mononuclear cell (PBMC)		Visit 1 day
mRNA levels in severe asthmatics as analyzed by gene profiling analysis	Messenger ribonucleic acid (mRNA) expression levels for blood leukocyte proteins.	Visit 1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with elevated LDG levels in severe asthmatics using gene profiling analysis on a single PAXgene tube sample		Visit 1 day
Serum samples will be collected and analyzed for measurement of total IgE	Correlation between LDG in severe asthma and biomarkers identified in gene profiling analysis	Visit 1 day

Collaborators and Investigators

• Sponsor: Rush University Medical Center
• Collaborators: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): September 26, 2018
• Study Completion (Actual): December 16, 2020

Study Registration Dates

• First Submitted: July 6, 2015
• First Submitted That Met QC Criteria: January 19, 2016
• First Posted (Estimate): January 20, 2016

Study Record Updates

• Last Update Posted (Actual): February 11, 2022
• Last Update Submitted That Met QC Criteria: February 10, 2022
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Asthma
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: ML29345