Respiratory Microbiota and Immune Response in CVID

Study Overview
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Brief Summary
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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.

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

Conditions
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CVID

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Antibody deficient participants<br>Provider referred patients that have antibody deficiency. | |
| Controls<br>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?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary biology, RNAseq analysis, Impaired antibody response, Pattern recognition receptor, Immunoglobulins, Respiratory microbiota, Nuclear Factor Kappa B (NF-κB)-driven cytokines, Complex microbial-host cell interactions