Abstract

DOCK8 deficiency is a combined immunodeficiency disease that is characterized by severe problems with recurrent, persistent, and progressive infections, especially of the skin. This is a major contributing factor to the high morbidity and mortality seen in this disease. However, another key feature of DOCK8 deficiency is the allergic disease: patients typically have severe eczematous dermatitis, asthma, and life-threatening food allergies, often accompanied by high levels of serum IgE and eosinophilia. Rarer complications include vasculopathy, cancer, and autoimmunity. In FY2018, we contributed to a reports which are currently under review investigating the viromes of DOCK8-deficientt patients and accumulated posttransplant outcomes. We have continued our investigations examining genotype-phenotype relationships of this disease, as well as collaborations investigating mechanisms of allergic manifestations of disease and outcomes after transplantation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI001193-05
Application #
9786491
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2018
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
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  Publications

Tangye, Stuart G; Pillay, Bethany; Randall, Katrina L et al. (2017) Dedicator of cytokinesis 8-deficient CD4(+) T cells are biased to a TH2 effector fate at the expense of TH1 and TH17 cells. J Allergy Clin Immunol 139:933-949
Dimitriades, Victoria R; Devlin, Vincent; Pittaluga, Stefania et al. (2017) DOCK 8 Deficiency, EBV+ Lymphomatoid Granulomatosis, and Intrafamilial Variation in Presentation. Front Pediatr 5:38
Shah, Nirali N; Freeman, Alexandra F; Su, Helen et al. (2017) Haploidentical Related Donor Hematopoietic Stem Cell Transplantation for Dedicator-of-Cytokinesis 8 Deficiency Using Post-Transplantation Cyclophosphamide. Biol Blood Marrow Transplant 23:980-990
Freeman, Alexandra F; Shah, Nirali N; Parta, Mark et al. (2016) Haploidentical related donor hematopoietic stem cell transplantation with post-transplantation cyclophosphamide for DOCK8 deficiency. J Allergy Clin Immunol Pract 4:1239-1242.e1
Zhang, Qian; Jing, Huie; Su, Helen C (2016) Recent Advances in DOCK8 Immunodeficiency Syndrome. J Clin Immunol 36:441-9
Happel, Corinne S; Stone, Kelly D; Freeman, Alexandra F et al. (2016) Food allergies can persist after myeloablative hematopoietic stem cell transplantation in dedicator of cytokinesis 8-deficient patients. J Allergy Clin Immunol 137:1895-1898.e5
Cuellar-Rodriguez, Jennifer; Freeman, Alexandra F; Grossman, Jennifer et al. (2015) Matched related and unrelated donor hematopoietic stem cell transplantation for DOCK8 deficiency. Biol Blood Marrow Transplant 21:1037-45
Aydin, Susanne E; Kilic, Sara Sebnem; Aytekin, Caner et al. (2015) DOCK8 deficiency: clinical and immunological phenotype and treatment options - a review of 136 patients. J Clin Immunol 35:189-98
Betts, K; Abusleme, L; Freeman, A F et al. (2015) A 17-year old patient with DOCK8 deficiency, severe oral HSV-1 and aggressive periodontitis - a case of virally induced periodontitis? J Clin Virol 63:46-50
Zhang, Qian; Dove, Christopher G; Hor, Jyh Liang et al. (2014) DOCK8 regulates lymphocyte shape integrity for skin antiviral immunity. J Exp Med 211:2549-66

Showing the most recent 10 out of 14 publications