Combined Immunodeficiency Associated with DOCK8 Mutations and Related Immunodeficiencies

Studying rare inherited immune disorders in patients has led to improved understanding of how the human immune system is fundamentally regulated. This knowledge is needed to develop new therapeutic agents for immunodeficiency, autoimmunity, cancer, and transplantation. One such illustrative disorder is DOCK8 deficiency, whose molecular etiology was discovered only in the past year. The discovery of autosomal recessive DOCK8 mutations and the identification of associated biomarkers have identified new areas of research and have also provided insights into similar and potentially related disorders, including the pathogenesis of certain associated viral infections. These developments are discussed in the eight reviews that are brought together in this special issue of Disease Markers. In the first review, Alexandra Freeman and Steven Holland compare and contrast the clinical features of hyper-IgE syndrome due to STAT3, TYK2, and DOCK8 mutations. These three conditions were originally grouped as a single disease entity based primarily upon shared clinical findings of elevated serum IgE, eczema,