Clinical, genetic and immunological study of human adenosine deaminase type 2 deficiency

Human adenosine deaminase type 2 (ADA2) deficiency is a recently described inborn error of immunity with a broad presentation including fever with cutaneous vasculitis but also intracranial hemorrhages, immunodeficiency and bone marrow anomalies. It carries important morbidity and substantial mortality (10%). Bi-allelic mutations in the gene ADA2 are responsible for this rare condition. The gene product, adenosine deaminase 2, plays a role in the control of inflammation. In this project, we will study in depth the mutations causing ADA2 deficiency and the clinical and immunological picture. Next we will perform in-depth immunological studies. We will investigate the underlying mechanisms that lead to increased susceptibility to viral infections, both herpes virus infections as well as cutaneous warts infections. Finally, several conditions in medicine mimic ADA2 deficiency. Hence, we will focus on the potential implication of secondary ADA2 deficiency in conditions where the main cellular source of ADA2 is absent (monocytes and macrophages) as in prolonged monocytopenia and neutropenia post-transplantation. In these circumstances ADA2 deficiency may contribute to fever and inflammation. In all, the results of the scientific work in this project may aid in the management of both patients with ADA2 deficiency as well as patients suffering from a variety of other conditions.