ArticleBlood advances2021
Lentiviral correction of enzymatic activity restrains macrophage inflammation in adenosine deaminase 2 deficiency.
Article in Blood advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 of them syntheses that pooled it.
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Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 35 citations in OpenAlex.
- Newborn screening for severe combined immunodeficiency in the NHS newborn blood spot screening programme: a systematic review.Health technology assessment (Winchester, England) · 2026Pooled it
- A wide spectrum of phenotype of deficiency of deaminase 2 (DADA2): a systematic literature review.Orphanet journal of rare diseases · 2023Pooled it
- ADA2 genotype and enzyme activity may predict vasculitic or hematologic DADA2 phenotype.Journal of human immunity · 2026Article
- Adenosine deaminase type 2 deficiency: From rare to common.Journal of human immunity · 2026Review
- Gene therapy supports long-term reconstitution of patient hematopoietic stem cells in deficiency of adenosine deaminase 2.Molecular therapy. Methods & clinical development · 2025Article
- Chimeric enzymes enhance treatment potential for globoid cell leukodystrophy through hematopoietic stem cell gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- The pathogenesis, clinical presentations and treatment of monogenic systemic vasculitis.Nature reviews. Rheumatology · 2025Review
- Deficiency of adenosine deaminase 2 (DADA2) with recurrent ischemic stroke, fever and cutaneous changes: A case report.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Article
- Getting to know adenosine deaminase 2 deficiency inside and out.The Journal of allergy and clinical immunology · 2025Review
- Intracellular concentration of ADA2 is a marker for monocyte differentiation and activation.Frontiers of medicine · 2025Article
- Key Genes Associated With Functional Specialization of Neonatal Peripheral Monocytes.Human mutation · 2025Article
- [Advances in gene therapy for inborn errors of immunity].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2024Review
- ADA2 regulates inflammation and hematopoietic stem cell emergence via the ACommunications biology · 2024Article
- Neurological phenotype of adenosine deaminase 2 deficient patients: a cohort study.European journal of neurology · 2024Article
- Cellular models in autoinflammatory disease research.Clinical & translational immunology · 2024Review
- A case series of ten plus one deficiency of adenosine deaminase 2 (DADA2) patients in Iran.Pediatric rheumatology online journal · 2023Article
- Deficiency of adenosine deaminase 2: a challenging differential diagnosis of polyarteritis nodosa.Reumatologia · 2023Review
- Case Report: Interindividual variability and possible role of heterozygous variants in a family with deficiency of adenosine deaminase 2: are all heterozygous born equals?Frontiers in immunology · 2023Article
- A novel frameshift variant in the ADA2 gene of a patient with a neurological phenotype: a case report.Pediatric rheumatology online journal · 2022Article
- Mechanisms of vascular inflammation in deficiency of adenosine deaminase 2 (DADA2).Seminars in immunopathology · 2022Review
Corrections and comments
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Authors and funding
25 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adenosine deaminase 2 deficiency (DADA2) is a rare inherited disorder that is caused by autosomal recessive mutations in the ADA2 gene. Clinical manifestations include early-onset lacunar strokes, vasculitis/vasculopathy, systemic inflammation, immunodeficiency, and hematologic defects. Anti-tumor necrosis factor therapy reduces strokes and systemic inflammation. Allogeneic hematopoietic stem/progenitor cell (HSPC) transplantation can ameliorate most disease manifestations, but patients are at risk for complications. Autologous HSPC gene therapy may be an alternative curative option for patients with DADA2. We designed a lentiviral vector encoding ADA2 (LV-ADA2) to genetically correct HSPCs. Lentiviral transduction allowed efficient delivery of the functional ADA2 enzyme into HSPCs from healthy donors. Supranormal ADA2 expression in human and mouse HSPCs did not affect their multipotency and engraftment potential in vivo. The LV-ADA2 induced stable ADA2 expression and corrected the enzymatic defect in HSPCs derived from DADA2 patients. Patients' HSPCs re-expressing ADA2 retained their potential to differentiate into erythroid and myeloid cells. Delivery of ADA2 enzymatic activity in patients' macrophages led to a complete rescue of the exaggerated inflammatory cytokine production. Our data indicate that HSPCs ectopically expressing ADA2 retain their multipotent differentiation ability, leading to functional correction of macrophage defects. Altogether, these findings support the implementation of HSPC gene therapy for DADA2.
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