Impaired Response to Polysaccharide Vaccine in Selective IgE Deficiency

Area of Science:

• Immunology
• Clinical Immunology
• Genetics

Background:

• Immunoglobulin E deficiency (IgED) is associated with primary antibody deficiency (PAD).
• Selective IgED (sIgED) may be a more sensitive predictor of PAD development than declining IgG.
• IgE production involves two class switch recombination (CSR) events, unlike IgG.

Purpose of the Study:

• To investigate if sIgED is a more sensitive predictor of emerging PAD than declining IgG.
• To assess if sIgED is associated with impaired antibody responses to T-cell independent antigens.
• To determine if sIgED is linked to aberrant induction of germline transcripts in B-cells.

Main Methods:

• Compared polysaccharide vaccination responses in healthy individuals with sIgED and healthy controls (HCs).
• Assessed in vitro induction of germline and IgE heavy chain transcripts in B-cells from sIgED patients and HCs.
• Stimulated B-cells with IL-4 + CD40L to analyze CSR machinery.

Main Results:

• 30% of sIgED patients had suboptimal vaccine responses, compared to 0% of HCs (p=0.017).
• sIgED individuals with abnormal vaccine responses showed persistent germline mRNA expression at day 5.
• Lower IgE heavy chain transcript levels were observed in sIgED patients with abnormal vaccine responses.

Conclusions:

• Patients with sIgED are prone to abnormal antibody responses to T cell-independent antigens.
• Dysregulated CSR machinery may be present in individuals with sIgED.
• Longitudinal monitoring of sIgED patients can aid in early PAD identification.