DOCK8 deficiency: Insights into pathophysiology, clinical features and management

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


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.

Publication types

  • Review

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Active Transport, Cell Nucleus
  • Adaptive Immunity / immunology
  • Autoimmune Diseases / immunology*
  • Cell Movement / immunology
  • Cell Survival
  • Eczema / immunology
  • Epstein-Barr Virus Infections
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / immunology*
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Hypersensitivity / immunology*
  • Immunity, Innate / immunology
  • Immunologic Deficiency Syndromes / genetics
  • Immunologic Deficiency Syndromes / immunology*
  • Immunologic Deficiency Syndromes / therapy
  • Infections
  • Inflammation / immunology
  • Neoplasms / immunology*
  • Neoplasms / virology
  • Papillomavirus Infections
  • Recurrence
  • Respiratory Tract Diseases / immunology
  • STAT3 Transcription Factor / metabolism
  • Skin Diseases, Viral / immunology


  • DOCK8 protein, human
  • Guanine Nucleotide Exchange Factors
  • STAT3 Transcription Factor