ArticlePediatric rheumatology online journal2014
Mutations in CECR1 associated with a neutrophil signature in peripheral blood.
Article in Pediatric rheumatology online journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.
- A wide spectrum of phenotype of deficiency of deaminase 2 (DADA2): a systematic literature review.Orphanet journal of rare diseases · 2023Pooled it
- Adenosine deaminase type 2 deficiency: From rare to common.Journal of human immunity · 2026Review
- ADA2-deficient cells exhibit increased levels of cell death and metabolic disturbances.Cell death discovery · 2026Article
- Dominant negative ADA2 mutations cause ADA2 deficiency in heterozygous carriers.The Journal of experimental medicine · 2025Article
- Inhibition of lysosomal degradation increases expression of mutant ADA2 in DADA2 monocytes.The Journal of allergy and clinical immunology · 2025Article
- The pathogenesis, clinical presentations and treatment of monogenic systemic vasculitis.Nature reviews. Rheumatology · 2025Review
- NET Proteomic Profiling Reveals New Pathways Potentially Implicated in Dendritic Cell-Mediated Inflammation in DADA2 Patients.Journal of clinical immunology · 2025Article
- Arterial and venous thrombosis in systemic and monogenic vasculitis.Nature reviews. Rheumatology · 2025Review
- Getting to know adenosine deaminase 2 deficiency inside and out.The Journal of allergy and clinical immunology · 2025Review
- A Clinical Case Report of Deficiency of Adenosine Deaminase 2 Syndrome (DADA 2) Presenting as a Brachial Artery Aneurysm.Mediterranean journal of rheumatology · 2025Article
- Autoinflammation in patients with leukocytic CBL loss of heterozygosity is caused by constitutive ERK-mediated monocyte activation.The Journal of clinical investigation · 2024Article
- Human ADA2 Deficiency: Ten Years Later.Current allergy and asthma reports · 2024Review
- Inborn Errors of Purine Salvage and Catabolism.Metabolites · 2023Review
- Kidney Involvement in Autoinflammatory Diseases.Kidney diseases (Basel, Switzerland) · 2023Review
- Vasculitis and vasculopathy associated with inborn errors of immunity: an overview.Frontiers in pediatrics · 2023Review
- Deficiency of adenosine deaminase 2: a challenging differential diagnosis of polyarteritis nodosa.Reumatologia · 2023Review
- Co-expression network analysis identifies potential candidate hub genes in severe influenza patients needing invasive mechanical ventilation.BMC genomics · 2022Article
- Mechanisms of vascular inflammation in deficiency of adenosine deaminase 2 (DADA2).Seminars in immunopathology · 2022Review
- Atypical presentation of adenosine deaminase 2 deficiency with bi-allelic ADA2 mutation.Clinical case reports · 2022Article
- Adenosine deaminase, not immune to a mechanistic rethink in central nervous system disorders?Histology and histopathology · 2022Review
Corrections and comments
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Authors and funding
18 authors at 8 institutions in 3 countries.
Funding
Abstract
backgroundA reduction of ADA2 activity due to autosomal recessive loss of function mutations in CECR1 results in a newly described vasculopathic phenotype reminiscent of polyarteritis nodosa, with manifestations ranging from fatal systemic vasculitis with multiple strokes in children to limited cutaneous disease in middle-aged individuals. Evidence indicates that ADA2 is essential for the endothelial integrity of small vessels. However, CECR1 is not expressed, nor is the ADA2 protein detectable, in cultured human endothelial cells, thus implicating additional cell types or circulating factors in disease pathogenesis.
methodsConsidering the phenotypic overlap of ADA2 deficiency with the type I interferonopathy Aicardi-Goutières syndrome due to mutations in SAMHD1, we looked for the presence of an interferon signature in the peripheral blood of two newly ascertained ADA2-deficient patients.
resultsWe identified biallelic CECR1 mutations in two patients consistent with ADA2 deficiency. Both patients demonstrated an upregulation of interferon stimulated gene transcripts in peripheral blood. More strikingly however, genome-wide analysis revealed a marked overexpression of neutrophil-derived genes, suggesting that the vasculitis seen in ADA2 deficiency may be an indirect effect resulting from chronic and marked activity of neutrophils.
conclusionsWe hypothesise that ADA2 may act as a regulator of neutrophil activation, and that a reduction of ADA2 activity results in significant endothelial damage via a neutrophil-driven process.
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Registered trials
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