title: DOCK8 deficiency.
abstract: The discovery that loss-of-function mutations in the gene DOCK8 are responsible for most forms of autosomal recessive hyper-IgE syndrome and some forms of combined immunodeficiency without elevated serum IgE has led to studies into the immunopathogenesis of this disease. In this review, we relate the clinical features of this disease to studies using patients' cells and a mouse model of Dock8 deficiency, which have revealed how DOCK8 regulates T and B cell numbers and functions. The results of these studies help to explain how the absence of DOCK8 contributes to patients' susceptibility to viral, fungal, and bacterial infections. However, unanswered questions remain regarding how the absence of DOCK8 also leads to high IgE and allergic disease, predisposition for malignancy, and unusual clinical features, such as CNS abnormalities and autoimmunity, observed in some patients.
authors.affiliation: Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1546, USA.
authors.forename: Helen C
authors.initials: HC
authors.lastname: Su
authors.forename: Huie
authors.initials: H
authors.lastname: Jing
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002493:Central Nervous System Diseases / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology; D007589:Job Syndrome / Q000235:genetics / Q000276:immunology; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: C516591:DOCK8 protein, human; C545324:Dock8 protein, mouse; D020662:Guanine Nucleotide Exchange Factors; D007073:Immunoglobulin E