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Primary Immunodeficiency Diseases
Published in Donald Rudikoff, Steven R. Cohen, Noah Scheinfeld, Atopic Dermatitis and Eczematous Disorders, 2014
Adam Friedman, Manju Chacko Dawkins, Donald Rudikoff
Patients with DOCK8 deficiency develop elevated IgE, eczema, skin and sinopulmonary infections associated with severe cutaneous viral infections such as warts, molluscum contagiosum, serious herpes simplex virus or herpes zoster infections, and a predisposition to squamous cell carcinoma and other malignancies at a young age (Zhang et al. 2009).
Herpes Simplex Conjunctivitis and Recurrent Chalazia in a Patient DOCK8 Deficiency
Published in Ocular Immunology and Inflammation, 2022
Tinh Le, Basak Can, Faruk Orge
The Dedicator of Cytokinesis 8 (DOCK8) gene codes for a GEF protein that binds and activates Rho GTPases that regulate cytoskeletal structure, thereby playing a crucial role in processes such as homing, cytokine secretion, motility, and cytoskeletal organization.12 As such, DOCK8 deficiency can cause multiple defects in both the innate and adaptive immune systems. In the innate immune system, DOCK8 signaling is involved in NK cell-target cell binding and in clustering of cytolytic granules.13 In the adaptive immune system, DOCK8 deficiencies interfere with both humoral and cell-mediated immunity. In B cells, DOCK8 signaling plays a role in polarization of adhesion molecules upon antigen presentation, allowing for immune synapse formation and isotype switching.12 Disruption of this process is reflected in the fact that DOCK8 deficiency patients often generate poor immune responses after vaccination.14 Studies have also shown decreased numbers of circulating naive T cells in DOCK8 patients, as well as impaired CD8 T cell expansion, activation, and antiviral cytokine expression.15,16 Additionally, defects in cytokine and transcription factor expression crucial to Th17 cell differentiation have been suggested.14 These findings suggest multiple mechanisms underlying the susceptibility of DOCK8-deficient patients to viral skin infections, including diminished numbers of naive T cells, impaired CD8 T cell expansion and antiviral cytokine expression, and defective CD8 T cell migration to the skin surface, leading to a deficit in resident T cells in the skin. This patient’s history of disseminated cutaneous warts and cutaneous HSV infection are characteristic of the DOCK8 deficiency phenotype.