ArticleThe Journal of allergy and clinical immunology2014
B-cell development and functions and therapeutic options in adenosine deaminase-deficient patients.
Article in The Journal of allergy and clinical immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 32 citations in OpenAlex.
- Cytoreductive conditioning intensity predicts clonal diversity in ADA-SCID retroviral gene therapy patients.Blood · 2017Trial
- Trial
- B-cell reconstitution after lentiviral vector-mediated gene therapy in patients with Wiskott-Aldrich syndrome.The Journal of allergy and clinical immunology · 2015Trial
- A guide to B cell metabolism.Nature reviews. Immunology · 2026Review
- Nonconditioned ADA-SCID gene therapy reveals ADA requirement in the hematopoietic system and clonal dominance of vector-marked clones.Molecular therapy. Methods & clinical development · 2021Article
- Normal IgH Repertoire Diversity in an Infant with ADA Deficiency After Gene Therapy.Journal of clinical immunology · 2021Article
- National Institutes of Health-Defined Chronic Graft-vs.-Host Disease in Pediatric Hematopoietic Stem Cell Transplantation Patients Correlates With Parameters of Long-Term Immune Reconstitution.Frontiers in immunology · 2019Article
- Circular RNAs in immune responses and immune diseases.Theranostics · 2019Review
- Autonomous role of Wiskott-Aldrich syndrome platelet deficiency in inducing autoimmunity and inflammation.The Journal of allergy and clinical immunology · 2018Article
- A map of human circular RNAs in clinically relevant tissues.Journal of molecular medicine (Berlin, Germany) · 2017Article
- Multiparametric Whole Blood Dissection: A one-shot comprehensive picture of the human hematopoietic system.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2017Article
- Long-Term Outcome of Adenosine Deaminase-Deficient Patients-a Single-Center Experience.Journal of clinical immunology · 2017Article
- Adenosine Deaminase Deficiency - More Than Just an Immunodeficiency.Frontiers in immunology · 2016Review
- Diagnosis, Treatment and Long-Term Follow Up of Patients with ADA Deficiency: a Single-Center Experience.Journal of clinical immunology · 2015Article
- Longitudinal Evaluation of Immune Reconstitution and B-cell Function After Hematopoietic Cell Transplantation for Primary Immunodeficiency.Journal of clinical immunology · 2015Article
- Clinical applications of gene therapy for primary immunodeficiencies.Human gene therapy · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 8 institutions in 4 countries.
Funding
Abstract
backgroundAdenosine deaminase (ADA) deficiency causes severe cellular and humoral immune defects and dysregulation because of metabolic toxicity. Alterations in B-cell development and function have been poorly studied. Enzyme replacement therapy (ERT) and hematopoietic stem cell (HSC) gene therapy (GT) are therapeutic options for patients lacking a suitable bone marrow (BM) transplant donor.
objectiveWe sought to study alterations in B-cell development in ADA-deficient patients and investigate the ability of ERT and HSC-GT to restore normal B-cell differentiation and function.
methodsFlow cytometry was used to characterize B-cell development in BM and the periphery. The percentage of gene-corrected B cells was measured by using quantitative PCR. B cells were assessed for their capacity to proliferate and release IgM after stimulation.
resultsDespite the severe peripheral B-cell lymphopenia, patients with ADA-deficient severe combined immunodeficiency showed a partial block in central BM development. Treatment with ERT or HSC-GT reverted most BM alterations, but ERT led to immature B-cell expansion. In the periphery transitional B cells accumulated under ERT, and the defect in maturation persisted long-term. HSC-GT led to a progressive improvement in B-cell numbers and development, along with increased levels of gene correction. The strongest selective advantage for ADA-transduced cells occurred at the transition from immature to naive cells. B-cell proliferative responses and differentiation to immunoglobulin secreting IgM after B-cell receptor and Toll-like receptor triggering were severely impaired after ERT and improved significantly after HSC-GT.
conclusionsADA-deficient patients show specific defects in B-cell development and functions that are differently corrected after ERT and HSC-GT.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.