Understanding DOCK8 Function in Health and Human Disease

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

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 FY2025, we continued our collaborations with other NIH investigators examining microbial pathogenesis, genotype-phenotype relationships, and hematopoietic stem cell transplantation outcome in DOCK8-deficient patients. The results of a prospective clinical trial involving 36 patients at the NIH Clinical Center established that hematopoietic cell transplantation was both safe and effective in curing the disease. This study was particularly informative because compared to other centers, the NIH Clinical Center is typically referred more complicated and older patients for treatment, who may have a different clinical course during treatment. A complementary study, also involving the same patient cohort, demonstrated that hematopoietic cell transplantion was effective in reducing human papillomavirus and Staphylococcus aureus burdens in the skin, restoring the microbiome to normal, and resolving the viral warts and eczema in the skin in the transplanted DOCK8-deficient patients. Thus, these studies are important in establishing the standard for medical care in patients with this inborn error of immunity.