Insights into immunity from clinical and basic science studies of DOCK8 immunodeficiency syndrome.

Abstract

DOCK8 immunodeficiency syndrome (DIDS) is a progressive combined immunodeficiency that can be distinguished from other combined immunodeficiencies or hyperimmunoglobulinemia E syndromes in featuring (a) profound susceptibility to virus infections of the skin, with associated skin cancers, and (b) severe food allergies. The DOCK8 locus has many repetitive sequence elements that predispose to the generation of large germline deletions as well as recombination-mediated somatic DNA repair. Residual DOCK8 protein contributes to the variable disease phenotype. The severe virus infections of the skin, and probably also VZV-associated vasculopathy, reflect an important function of DOCK8, which is normally required to maintain lymphocyte shape integrity as the cells migrate through dense tissues. Loss of DOCK8 also causes immune deficits through other mechanisms including a milder generalized cell survival defect and skewing of T helper cell subsets. Recent work has uncovered the roles for DOCK8 in dendritic cell responses that can also help explain the virus susceptibility, as well as in regulatory T cells that might help explain autoimmunity in a minority of patients. Fortunately, hematopoietic stem cell transplantation cures the eczema and infection susceptibility of DIDS, but not necessarily the other disease manifestations including food allergies.

• Authors: Helen C Su, Huie Jing, Pam Angelus, Alexandra F Freeman
• Journal: Immunological reviews (Immunol Rev) Vol. 287 Issue 1 Pg. 9-19 (01 2019) ISSN: 1600-065X [Electronic] England
• PMID: 30565250 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Review)
• Copyright: Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

Chemical References

• DOCK8 protein, human
• Guanine Nucleotide Exchange Factors

Topics

• Clustered Regularly Interspaced Short Palindromic Repeats
• Disease Susceptibility
• Eczema
• Genetic Therapy
• Guanine Nucleotide Exchange Factors (genetics)
• Hematopoietic Stem Cell Transplantation
• Humans
• Immunologic Deficiency Syndromes (genetics, immunology, therapy)
• Neoplasms, Squamous Cell
• Pneumonia
• T-Lymphocytes (immunology)
• Vasculitis, Central Nervous System