The Child with Elevated IgE and Infection Susceptibility
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PEDIATRIC ALLERGY AND IMMUNOLOGY (W DOLEN, SECTION EDITOR)
The Child with Elevated IgE and Infection Susceptibility Alexandra F. Freeman 1 & Joshua D. Milner 2
# This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2020
Abstract Purpose of Review Over the last 13 years, the genetic etiologies have been determined for multiple conditions causing elevated serum IgE, infection susceptibilities, and variable other features. In this review, we discuss the clinical presentation, laboratory features, and genetics of these diseases caused by mutations in STAT3, DOCK8, PGM3, IL6ST, ZNF341, IL6R, IL6ST, CARD11, and CARD14, with particular focus given to STAT3LOF and DOCK8 deficiency. Recent Findings Defining the phenotype of each of these syndromes with high IgE and infection susceptibility shows that some have a pronounced connective tissue phenotype such as STAT3LOF and IL6ST deficiency, some have worse viral susceptibility such as DOCK8 deficiency and heterozygous LOF CARD11, and some have more severe allergy and eczema such as LOF CARD14. Summary Studying these distinct but overlapping monogenic diseases will allow a better understanding of more common disease processes such as allergy, eczema, infection susceptibility, scoliosis, and aneurysm. Keywords Hyper IgE syndrome . IgE . STAT3 . ZNF341 . DOCK8 . PGM3 . CARD11 . CARD14 . IL6ST . IL6R
Introduction Elevated serum IgE occurs in many conditions of immune dysregulation, with atopic disease being the most common. Primary immune deficiencies previously referred to as hyper IgE syndromes were defined by the constellation of eczema, recurrent infections, and elevated serum IgE. Over the last 13 years, multiple monogenic diseases that share these clinical findings have been defined, with each being a distinct disease, with specific clinical considerations and, for some, therapeutic interventions. It is no longer as meaningful to define these diseases as HIES, or by whether they are autosomal dominant or autosomal recessive “versions”, but rather by the more This article is part of the Topical Collection on Pediatric Allergy and Immunology * Alexandra F. Freeman [email protected] 1
National Institute of Allergy and Infectious Diseases, National Institutes of Health, NIH Building 10 Room 12C103, 9000 Rockville Pike, Bethesda, MD 20892, USA
2
Division of Allergy, Immunology and Rheumatology, Columbia University Medical Center, New York-Presbyterian Morgan Stanley Children’s Hospital, New York, NY, USA
specific and meaningful genetic causes, when known. That said, some of these disorders do have phenotypic similarities which in some cases are likely due to mutations within a particular pathway, and as such in understanding patients with elevated IgE and infection—whether due to a known or yet to be discovered cause, it is important to recognize the types of phenotypic features which may appear and cluster. In this review, we will discuss the main clinical features of genetically defined immune dysregula
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