Reviews and feature articlePrimary immune deficiencies with aberrant IgE production
Section snippets
Molecular basis of isotype switching to IgE
Pre-B cells go through VH-D-JH recombination in which individual heavy-chain variable (VH), diversity (D), and joining (JH) exons randomly combine and encode the antigen-specific VH domain. In naive B cells, the recombined VH-D-JH cassette lies upstream of the constant (C) μ exons, leading to IgM production. On stimulation, mature B cells undergo class switch recombination (CSR). Each constant heavy chain (CH) gene, except Cδ, is preceded by specialized DNA sequences with tandem repeats, called
PIDs with elevated IgE
Gene defects, mechanism of immune deficiency, and mechanism of IgE elevation of PIDs mentioned in this section are listed in Table II.
Conclusion
Three of the PIDs associated with high levels of IgE (IPEX, WAS, and Omenn syndrome) display a defective Treg cell number or function, which results in autoimmunity and a TH2 phenotype with increased IgE levels. HSCT is the standard curative therapy for IPEX, WAS, and Omenn syndrome and results in normalization of immune function and of serum IgE levels. HSCT recipients might have a lower risk of GVHD if the donor cells are enriched with Treg cells. The underlying cause of elevated IgE in HIES
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(Supported by an educational grant from Merck & Co., Inc.)
Series editors: Joshua A. Boyce, MD, Fred Finkelman, MD, William T. Shearer, MD, PhD, and Donata Vercelli, MD
Supported by National Institutes of Health grants P01-AI-031541 and P01-AI-076210.
Terms in boldface and italics are defined in the glossary on page 1055.