Respiratory Microbiota and Immune Response in CVID

NCT06173128 | Completed

• 1 other identifier: H-42779
• Study Type: observational
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

CVID

Keywords

Impaired antibody response; Pattern recognition receptor; Immunoglobulins; Respiratory microbiota; Nuclear Factor Kappa B (NF-κB)-driven cytokines; Complex microbial-host cell interactions; Pulmonary biology; RNAseq analysis

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (2)

• Altered respiratory microbiota due to primary antibody deficiency

  2 years

• Altered gene expression due to primary antibody deficiency

  2 years

Study Arms (2)

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.

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Boston University: lead
• Takeda: collaborator

Study Sites (1)

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood, saliva, nasopharyngeal, and sputum samples will be collected. 50 ml of blood will be collected/participant.This collection of blood will constitute the study biological sample repository. Peripheral blood mononuclear cells (PBMCs) plasma samples will be used for flow cytometry, cell culture, and enzyme-linked immunosorbent assays. RNAseq will be done on nasopharyngeal samples. Sputum samples will have measurement of lymphocyte subsets (by flow cytometry), cytokines and immunoglobulins (by multiplex ELISA), and RNA (both bacterial and host by RNA sequencing) in the laboratory.

Study Officials

• Paul J Maglione, MD PhD

  Boston University Chobanian & Avedisian School of Medicine, Pulmonary Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2023
• First Posted: December 15, 2023
• Study Start: March 15, 2024
• Primary Completion: February 15, 2026
• Study Completion: February 15, 2026
• Last Updated: March 6, 2026

Record last verified: 2026-03

Locations

US (1)