Undetectable IgE as a Sentinel Biomarker for Humoral Immunodeficiency

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.

Study Overview

• Status: Completed
• Conditions: Immune Deficiency
• Intervention / Treatment: Biological: Salmonella typhi polysaccharide vaccine

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

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vaccine; Subjects who meet enrollment criteria will be administered a single intramuscular dose of the Salmonella typhi polysaccharide vaccine	Biological: Salmonella typhi polysaccharide vaccine; Salmonella typhi polysaccharide vaccine; 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

Collaborators and Investigators

• Sponsor: University of Virginia
• Collaborators: CSL Behring; Jeffrey Modell Foundation
• Investigators: Principal Investigator: Larry Borish, MD, University of Virginia

Publications and helpful links

General Publications

• Lawrence MG, Palacios-Kibler TV, Workman LJ, Schuyler AJ, Steinke JW, Payne SC, McGowan EC, Patrie J, Fuleihan RL, Sullivan KE, Lugar PL, Hernandez CL, Beakes DE, Verbsky JW, Platts-Mills TAE, Cunningham-Rundles C, Routes JM, Borish L. Low Serum IgE Is a Sensitive and Specific Marker for Common Variable Immunodeficiency (CVID). J Clin Immunol. 2018 Apr;38(3):225-233. doi: 10.1007/s10875-018-0476-0. Epub 2018 Feb 17.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2019
• Primary Completion (Actual): December 31, 2023
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: May 28, 2019
• First Submitted That Met QC Criteria: May 29, 2019
• First Posted (Actual): May 30, 2019

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: IgE; immunodeficiency
• Additional Relevant MeSH Terms: Immune System Diseases; Immunologic Deficiency Syndromes
• Other Study ID Numbers: 21453

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified IPD that underlie results in a publication will be made available upon request of another researcher or if required by the publisher
• IPD Sharing Time Frame: Starting 6 months after publication
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes