Clinical, Immunological and Functional Study of ADA2 deficiency

ADA2 deficiency is a devastating rare inherited disorder caused by biallelic deleterious mutations in the ADA2 gene. Clinical manifestations include vasculopathy ranging from cutaneous vasculopathy (livedo) to lacunar brain infarction. Moreover, patients can have bone marrow failure and immunodeficiency. While anti-TNF agents are usually effective in controlling vasculopathy, bone marrow failure and immunodeficiency are often refractory. In part, ineffective treatment is lacking because the pathophysiology of ADA2 deficiency is incompletely understood. The goal of this ERC funded project is to investigate the role of ADA2 deficiency in ill explained forms of immunodeficiency and bone marrow failure as well as acute neurological manifestations. To this end, we will conduct clinical studies, immunophenotyping, proteomics and genomics, and in depth functional studies of the monocyte-endothelium interaction as well as endothelium and monocyte characteristics in ADA2 deficiency in comparison with patients without ADA2 deficiency and healthy controls.