Document Detail


Dedicator of cytokinesis 8 (DOCK8) deficiency.
MedLine Citation:
PMID:  20864884     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE OF REVIEW: To describe a new combined primary immunodeficiency disease, previously known as autosomal recessive hyper-IgE syndrome, whose molecular basis was discovered in 2009.
RECENT FINDINGS: Two groups identified homozygous and compound heterozygous loss-of-function mutations in the Dedicator of cytokinesis 8 (DOCK8) gene in at least 30 patients who had been previously diagnosed with an atypical form of hyper-IgE syndrome. Absence of DOCK8 expression impairs T cell expansion in vitro, which could help explain the T cell lymphopenia and susceptibility to cutaneous viral infections observed in these patients. In mouse models of DOCK8 deficiency, absence of DOCK8 expression also impairs the generation of a durable secondary antibody response to specific antigens, which could account for the functional antibody abnormalities and recurrent sinopulmonary infections observed in the patients. Two patients have been cured of infectious complications after myeloablative allogeneic hematopoietic cell transplantation.
SUMMARY: The discovery of the molecular basis of this disease is expected to facilitate diagnosis and definitive treatment with hematopoietic cell transplantation. Further research is needed to understand how DOCK8 normally functions in lymphocytes and how DOCK8 deficiency leads to disease.
Authors:
Helen C Su
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural; Review    
Journal Detail:
Title:  Current opinion in allergy and clinical immunology     Volume:  10     ISSN:  1473-6322     ISO Abbreviation:  Curr Opin Allergy Clin Immunol     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-10-29     Completed Date:  2011-05-24     Revised Date:  2013-05-27    
Medline Journal Info:
Nlm Unique ID:  100936359     Medline TA:  Curr Opin Allergy Clin Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  515-20     Citation Subset:  IM    
Affiliation:
Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. hsu@niaid.nih.gov
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Proliferation
Disease Models, Animal
Guanine Nucleotide Exchange Factors / genetics,  immunology*
Humans
Immunity, Humoral / genetics
Infection
Job's Syndrome / genetics*,  immunology*,  physiopathology
Lymphopenia
Mice
Mutation / genetics*
T-Lymphocytes / immunology*
Grant Support
ID/Acronym/Agency:
ZIA AI001059-03/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/DOCK8 protein, human; 0/Guanine Nucleotide Exchange Factors
Comments/Corrections

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