Translational research into human adenosine deaminase type 2 deficiency

Human adenosine type 2 (ADA2) deficiency is a rare but devastating condition. The phenotype is complex and comprises vasculitis (ranging from cutaneous to intracerebral vasculitis with lacunar infarcts), immunodeficiency (recurrent bacterial or viral infections), bone marrow anomalies (cytopenia, aplasia) and cancer (lymphoma, leukemia). Mortality is 10%, affecting mostly children. Vasculitis responds well to anti-TNF treatment. However, treatment options for cytopenia and immunodeficiency are limited and hematopoietic stem cell transplantation is often needed. Unfortunately the pathophysiology of DADA2 is still elusive. With this research proposal, I aim to study  (1) the phenotype and genotype of ADA2 deficiency,  (2)  the significance of ADA2 deficiency in medical conditions that resemble ADA2 deficiency (so-called phenocopies) (3)  the role of ADA2 and the pathophysiology of ADA2 deficiency  (4)  and to develop new treatment strategies for ADA2 deficiency and its phenocopies.