Respiratory Microbiota and Immune Response in CVID

Alteration of Respiratory Microbiota and Local Immune Response in Common Variable Immunodeficiency

Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency. Respiratory ailments are the most frequent complications of CVID, with chronic pulmonary disease developing in 30-60% and even more experiencing frequent acute respiratory infections. This project aims to establish cutting-edge approaches to study pulmonary biology in CVID and apply novel bioinformatics strategies to study complex interactions among microbes and host cells by direct sampling of the respiratory tract. The central hypothesis for this research is that antibody (Ab) deficiency in CVID alters respiratory microbiota and host interactions to drive pulmonary disease.

Study Overview

• Status: Recruiting
• Conditions: CVID

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

• Study Contact: Name: Paul J Maglione, MD PhD; Phone Number: 617 358 0913; Email: pmaglion@bu.edu
• Study Contact Backup: Name: Matthew S Ware, MS; Phone Number: 765 437 1305; Email: msware@bu.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Recruiting
      • Boston Medical Center
      • Contact: Paul J Maglione, MD PhD; Phone Number: 617-358-0913; Email: pmaglion@bu.edu
      • Contact: Matthew S Ware, MS; Email: msware@bu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Participants will be enrolled from the Boston Medical Center allergy and immunology clinics and from healthy volunteers at the Boston University medical campus (BUMC). They will be assigned into one of two groups: antibody deficient patients and controls. Blood, nasopharyngeal swab, saliva, and sputum (if possible) samples will be collected from each participant, ideally on the same day.

Description

Inclusion Criteria:

• Patients with primary antibody deficiency diagnosed by their treating physician
• Controls will not have a diagnosis of immunodeficiency of any sort
• Male and female patients will be enrolled evenly

Exclusion Criteria:

• Patients who self identify as pregnant
• Patients with asthma or chronic obstructive pulmonary disease (COPD) that are not well controlled clinically

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Antibody deficient participants; Provider referred patients that have antibody deficiency.
Controls; Patients without antibody deficiency from the allergy and immunology clinic at Boston Medical Center and from healthy volunteers at the BU School of Medicine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of respiratory sample RNA sequencing (RNAseq) analysis	Quality control analysis of RNA samples collected from nasopharyngeal swabs for adequacy to perform RNA-seq analysis will be performed. This will be done using the Boston University (BU) Medical Campus RNA core facility bioanalyzer, which will assess for adequate RNA quality and quantity for RNA-seq	1 year
Analysis of saliva sampling	Saliva samples will be analyzed by enzyme-linked immunosorbent assay (ELISA) and multiplex analysis (Luminex) for levels of antibodies as well as cytokines and other inflammatory proteins.	2 years
Respiratory microbiota analysis by RNA-seq of nasopharyngeal samples	RNA-seq data derived from nasopharyngeal samples will undergo computational analysis to identify alterations of microbiota constituency.	2 years
Host gene expression analysis by RNA-seq of nasopharyngeal samples	RNA-seq data derived from nasopharyngeal samples will undergo computational analysis to identify alterations of host gene and pathway expression.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Altered respiratory microbiota due to primary antibody deficiency	RNA seq will be used to determine if primary antibody deficiency alters respiratory microbiota	2 years
Altered gene expression due to primary antibody deficiency	RNA seq will be used to determine if primary antibody deficiency alters host gene expression.	2 years

Collaborators and Investigators

• Sponsor: Boston University
• Collaborators: Takeda
• Investigators: Principal Investigator: Paul J Maglione, MD PhD, Boston University Chobanian & Avedisian School of Medicine, Pulmonary Center

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2024
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: December 7, 2023
• First Submitted That Met QC Criteria: December 7, 2023
• First Posted (Actual): December 15, 2023

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Immunoglobulins; Respiratory microbiota; Impaired antibody response; Pattern recognition receptor; Nuclear Factor Kappa B (NF-κB)-driven cytokines; Complex microbial-host cell interactions; Pulmonary biology; RNAseq analysis
• Other Study ID Numbers: H-42779

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No