[ADA2, an Adenosine Deaminase Isozyme Acting as a Regulator of Autoinflammation].

Abstract

Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive genetic disorder caused by loss-of-function mutations in the gene encoding adenosine deaminase (ADA) 2. This enzyme catalyzes the deamination reaction of adenosine/2'-deoxyadenosine to inosine/2'-deoxyinosine. DADA2 exhibits a complex clinical presentation, with systemic vasculitis with stroke, bone marrow failure, and immunodeficiency as the major pathologies. Since its discovery in 2014, more than 400 cases have been reported, and the phenotype has expanded significantly. DADA2 generally presents in childhood, although diagnosis in adulthood has also been reported, indicating the need to raise awareness of this disease beyond pediatrics. ADA2 is believed to be relevant in the regulation of the human immune system. Currently, knowledge is accumulating on the association between macrophage polarization into an inflammatory phenotype and systemic vasculitis, upregulation of the type I/II interferon pathway, and neutrophil function. The biochemical characteristics of ADA2 that differ from those of its isozyme ADA1 are a subject of significant research. One of these characteristics, N-glycosylation, plays a vital role in controlling the formation of the functional three-dimensional structure of ADA2. Moreover, with the accumulation of knowledge regarding the dysregulation of innate and adaptive immunity in DADA2 and the biochemical properties of ADA2, effective treatments and diagnostic methods are being established. This review provides an overview of ADA2 properties and DADA2.