title: Primary Immunodeficiencies with Elevated IgE.
abstract: In recent years a number of primary immunodeficiencies (PIDs) characterized by elevated Immunoglobulin E (IgE) levels have been uncovered and termed as Hyper-IgE syndrome (HIES). In addition to the elevated levels of IgE, patients with these PIDs display a spectrum of infections by staphylococci and fungi, and in some cases viruses, particularly affecting skin and lungs. Most of these PIDs also have a non-infectious phenotype, comprising musculoskeletal, vascular, and neurological abnormalities. The genetic basis for the majority of conditions with elevated IgE has now been established and includes mutations in STAT3, DOCK8, TYK2, and most recently PGM3 molecules. However, in some patients with the relevant phenotype, mutations in these molecules are not identified, suggesting additional genetic etiologies of HIES not yet discovered. As the immunological and molecular basis of HIES is being unraveled, important insights are emerging that may have implications for our understanding of basic principles of immunology and protective immunity as well as for the pathogenesis and clinical management of patients with these complex and challenging PIDs. In this review, are presented the current knowledge on the clinical presentation, infectious phenotype, and the genetic and immunological pathogenesis of hyper-IgE syndromes as well as some other PIDs with elevated levels of IgE.
authors.affiliation: a Department of Infectious Diseases, International Center for Immunodeficiency Diseases (ICID) , Aarhus University Hospital , Skejby , Aarhus , Denmark.
authors.forename: Trine H
authors.initials: TH
authors.lastname: Mogensen
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000935:Antifungal Agents / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016026:Bone Marrow Transplantation; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D003937:Diagnosis, Differential; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000378:metabolism*; D007589:Job Syndrome / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D009154:Mutation; D010641:Phenotype; D010733:Phosphoglucomutase / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016511:Severe Combined Immunodeficiency / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D053634:TYK2 Kinase / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000998:Antiviral Agents; D016207:Cytokines; C516591:DOCK8 protein, human; D020662:Guanine Nucleotide Exchange Factors; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D007073:Immunoglobulin E; D053634:TYK2 Kinase; C070139:TYK2 protein, human; C549916:PGM3 protein, human; D010733:Phosphoglucomutase
keywords: DOCK8; JAK-STAT signaling; STAT3; TYK2; atypical mycobacteriosis; chronic mucocutaneous candidiasis; herpes virus infections; hyper-IgE syndrome; primary immunodeficiency; staphylococcus aureus