Understanding DOCK8 Function in Health and Human Disease

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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 FY2023, work on this project was limited due to COVID-19 pandemic with limitations on staffing impacting non-COVID-19 projects as well as limitations on study subjects coming to the NIH Clinical Center. These limitations were gradually lifted as we continued our investigations examining genotype-phenotype relationships of this disease, as well as collaborations investigating cellular/molecular mechanisms of virus susceptibility, allergic manifestations of disease, and long-term effects of hematopoietic stem cell transplantation on natural history of disease.