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Journal of Clinical Immunology
Published in: Journal of Clinical Immunology 5/2018

Open Access 01-07-2018 | CME Review

Deficiency of Adenosine Deaminase 2 (DADA2): Updates on the Phenotype, Genetics, Pathogenesis, and Treatment

Authors: Isabelle Meyts, Ivona Aksentijevich

Published in: Journal of Clinical Immunology | Issue 5/2018

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Abstract

Deficiency of ADA2 (DADA2) is the first molecularly described monogenic vasculitis syndrome. DADA2 is caused by biallelic hypomorphic mutations in the ADA2 gene that encodes the adenosine deaminase 2 (ADA2) protein. Over 60 disease-associated mutations have been identified in all domains of ADA2 affecting the catalytic activity, protein dimerization, and secretion. Vasculopathy ranging from livedo reticularis to polyarteritis nodosa (PAN) and life-threatening ischemic and/or hemorrhagic stroke dominate the clinical features of DADA2. Vasculitis and inflammation can affect many organs, explaining the intestinal, hepatological, and renal manifestations. DADA2 should be primarily considered in patients with early-onset fevers, rashes, and strokes even in the absence of positive family history. Hematological manifestations include most commonly hypogammaglobulinemia, although pure red cell aplasia (PRCA), immune thrombocytopenia, and neutropenia have been increasingly reported. Thus, DADA2 may unify a variety of syndromes previously not thought to be related. The first-line treatment consists of TNF-inhibitors and is effective in controlling inflammation and in preserving vascular integrity. Hematopoietic stem cell transplantation (HSCT) has been successful in a group of patients presenting with hematological manifestations. ADA2 is highly expressed in myeloid cells and plays a role in the differentiation of macrophages; however, its function is still largely undetermined. Deficiency of ADA2 has been linked to an imbalance in differentiation of monocytes towards proinflammatory M1 macrophages. Future research on the function of ADA2 and on the pathophysiology of DADA2 will improve our understanding of the condition and promote early diagnosis and targeted treatment.
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Metadata
Title
Deficiency of Adenosine Deaminase 2 (DADA2): Updates on the Phenotype, Genetics, Pathogenesis, and Treatment
Authors
Isabelle Meyts
Ivona Aksentijevich
Publication date
01-07-2018
Publisher
Springer US
Published in
Journal of Clinical Immunology / Issue 5/2018
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-018-0525-8

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