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Clin Immunol. 2017 Aug;181:75-82. doi: 10.1016/j.clim.2017.06.003. Epub 2017 Jun 15.

DOCK8 deficiency: Insights into pathophysiology, clinical features and management.

Author information

1
Division of Immunology, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
2
Division of Pediatric Allergy and Immunology, Meram Medical Faculty, Necmettin Erbakan University, Konya, Turkey.
3
Division of Immunology, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA, USA. Electronic address: talal.chatila@childrens.harvard.edu.

Abstract

Dedicator of cytokinesis 8 (DOCK8) deficiency is a combined immunodeficiency that exemplifies the broad clinical features of primary immunodeficiencies (PIDs), extending beyond recurrent infections to include atopy, autoimmunity and cancer. It is caused by loss of function mutations in DOCK8, encoding a guanine nucleotide exchange factor highly expressed in lymphocytes that regulates the actin cytoskeleton. Additional roles of DOCK8 have also emerged, including regulating MyD88-dependent Toll-like receptor signaling and the activation of the transcription factor STAT3. DOCK8 deficiency impairs immune cell migration, function and survival, and it impacts both innate and adaptive immune responses. Clinically, DOCK8 deficiency is characterized by allergic inflammation as well as susceptibility towards infections, autoimmunity and malignancy. This review details the pathophysiology, clinical features and management of DOCK8 deficiency. It also surveys the recently discovered combined immunodeficiency due to DOCK2 deficiency, highlighting in the process the emerging spectrum of PIDs resulting from DOCK protein family abnormalities.

KEYWORDS:

Actin; CDC42; Combined immunodeficiency; DOCK2; DOCK8; Dedicator of cytokinesis; Hyper IgE syndrome; Primary immunodeficiency; RAC1; STAT3

PMID:
28625885
PMCID:
PMC5555255
DOI:
10.1016/j.clim.2017.06.003
[Indexed for MEDLINE]
Free PMC Article

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