Undetectable IgE as a Sentinel Biomarker for Humoral Immunodeficiency

Study Overview
=================
Brief Summary
-----------------
This study is trying to find out if an undetectable serum immunoglobulin E (IgE) is a biomarker, or early sign of, the development of immune deficiency.

Detailed Description
-----------------
IgE is the antibody thought to be responsible for developing allergies. Undetectable serum IgE (an IgE below the lower limit of detection) is found in about 3% of the general population. In the past, it has been thought that having an undetectable IgE does not have any health impact, other than meaning that you are at low risk for having allergies. However, recent studies of patients with undetectable IgE have shown higher rates of infections, autoimmune disease and cancer. Patients with an immune deficiency called common variable immunodeficiency (CVID) also have higher rates of infections, autoimmune disease and cancer. Recently, we have shown that most patients with CVID have a low/undetectable serum IgE. This study is trying to find out if an undetectable serum IgE is a biomarker, or early sign of, the development of CVID or other antibody deficiencies

Official Title
-----------------
Undetectable IgE as a Sentinel Biomarker for Humoral Immunodeficiency

Conditions
-----------------
Immune Deficiency

Intervention / Treatment
-----------------
* Biological: Salmonella typhi polysaccharide vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18-80 Willingness and ability to comply with scheduled visits and study procedures Undetectable serum IgE (defined as >2 IU/mL or the lower threshold of detection) Normal or high serum immunoglobulins (within or above laboratory reference range for IgG, IgA, and IgM) patients previously seen at the University of Virginia Asthma, Allergy, and Immunology clinics where undetectable serum IgE was noted Control subjects must have participated in study IRB#14457 (only applicable for healthy controls in epsilon germline transcript portion of the study) Exclusion Criteria: The following vulnerable populations will be excluded: pregnant women, fetuses, neonates, children, prisoners, cognitively impaired, educational or economically disadvantaged, non-English speaking subjects Known personal history of immunodeficiency Known personal history of recurrent infections Low serum immunoglobulins (below the laboratory reference range for IgG, IgA, or IgM) Recent or current treatment with systemic immunosuppression within the past 30 days

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vaccine<br>Subjects who meet enrollment criteria will be administered a single intramuscular dose of the Salmonella typhi polysaccharide vaccine | Biological: Salmonella typhi polysaccharide vaccine<br>* Salmonella typhi polysaccharide vaccine<br>* Other names: Typhim Vi;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vaccination response | IgG to Salmonella typhi will be measured, with a normal response calculated as at least a 2-fold increase in IgG titers post-vaccination | 4-6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Epsilon germline transcript production | B cells isolated from subjects will be evaluated to determine their ability to produce Epsilon germline transcript in response to stimulation | 3 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
immunodeficiency, IgE