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. 2023 Aug;43(6):1448-1454.
doi: 10.1007/s10875-023-01501-y. Epub 2023 May 12.

Impaired Response to Polysaccharide Vaccine in Selective IgE Deficiency

Emily Noonan  1 , Matthew D Straesser  1   2 , Thomas Makin  1 , Abigail Williams  1 , Amani Al-Hazaymeh  1 , John M Routes  3 , James Verbsky  3 , Larry Borish  1   4 , Monica G Lawrence  5   6
Affiliations

Impaired Response to Polysaccharide Vaccine in Selective IgE Deficiency

Emily Noonan et al. J Clin Immunol. 2023 Aug.

Abstract

Purpose: Immunoglobulin E deficiency (IgED) (defined as IgE < 2 IU/mL) is enriched in patients with primary antibody deficiency (PAD). We hypothesized that selective IgED (sIgED) is a more sensitive predictor of the development of PAD than declining IgG, as IgE production typically requires two class switch recombination (CSR) events in contrast to IgG. Thus, the inability of patients with sIgED to mount an appropriate antibody response to a T-cell independent antigen or evidence of aberrant induction of ɛ germ line (ɛGL) or IgE heavy chain (IgEHC) transcripts in vitro would support the concept that sIgED is a biomarker for emerging PAD.

Methods: We compared pre- and post-polysaccharide vaccination titers in healthy patients with sIgED without a history of recurrent infections or autoimmunity (n = 20) and in healthy controls (HCs) (n = 17). Subsequently, we assessed in vitro induction of εGL and IgEHC transcripts in patients with sIgED and HC (n = 6) in response to IL-4 + CD40L stimulation.

Results: Thirty percent of patients with sIgED did not have a robust vaccine response compared to 0% of HCs (p = 0.017). Individuals with sIgED with an abnormal vaccine response demonstrated persistent germline mRNA expression in their B-cells at day 5, with lower levels of IgEHC, compared to both HCs and sIgED participants with a normal vaccine response.

Conclusion: Patients with sIgED are more likely to have abnormal antibody responses to a T cell-independent antigen and may have dysregulated CSR machinery. Following individuals with sIgED longitudinally may be beneficial in the early identification of PAD.

Keywords: CVID; Hypogammaglobinemia; IgE; Immunodeficiency.

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