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PROMIDISα: A T-cell receptor α signature associated with immunodeficiencies caused by V(D)J recombination defects
- Source :
- Journal of Allergy and Clinical Immunology, Journal of Allergy and Clinical Immunology, Elsevier, 2019, 143 (1), pp.325-334.e2. ⟨10.1016/j.jaci.2018.05.028⟩, Journal of Allergy and Clinical Immunology, 2019, 143 (1), pp.325-334.e2. ⟨10.1016/j.jaci.2018.05.028⟩
- Publication Year :
- 2017
-
Abstract
- International audience; BACKGROUND:V(D)J recombination ensures the diversity of the adaptive immune system. Although its complete defect causes severe combined immunodeficiency (ie, T-B- severe combined immunodeficiency), its suboptimal activity is associated with a broad spectrum of immune manifestations, such as late-onset combined immunodeficiency and autoimmunity. The earliest molecular diagnosis of these patients is required to adopt the best therapy strategy, particularly when it involves a myeloablative conditioning regimen for hematopoietic stem cell transplantation.OBJECTIVE:We aimed at developing biomarkers based on analysis of the T-cell receptor (TCR) α repertoire to assist in the diagnosis of patients with primary immunodeficiencies with V(D)J recombination and DNA repair deficiencies.METHODS:We used flow cytometric (fluorescence-activated cell sorting) analysis to quantify TCR-Vα7.2-expressing T lymphocytes in peripheral blood and developed PROMIDISα, a multiplex RT-PCR/next-generation sequencing assay, to evaluate a subset of the TCRα repertoire in T lymphocytes.RESULTS:The combined fluorescence-activated cell sorting and PROMIDISα analyses revealed specific signatures in patients with V(D)J recombination-defective primary immunodeficiencies or ataxia telangiectasia/Nijmegen breakage syndromes.CONCLUSION:Analysis of the TCRα repertoire is particularly appropriate in a prospective way to identify patients with partial immune defects caused by suboptimal V(D)J recombination activity, a DNA repair defect, or both. It also constitutes a valuable tool for the retrospective in vivo functional validation of variants identified through exome or panel sequencing. Its broader implementation might be of interest to assist early diagnosis of patients presenting with hypomorphic DNA repair defects inclined to experience acute toxicity during prehematopoietic stem cell transplantation conditioning.
- Subjects :
- 0301 basic medicine
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology
Male
DCLRE1C
Receptors, Antigen, T-Cell, alpha-beta
DNA repair
Primary immunodeficiency
T-cell receptor α repertoire
V(D)J recombination
ataxia telangiectasia
next-generation sequencing
Adolescent
Adult
Child
Child, Preschool
Female
Humans
Infant
Infant, Newborn
Middle Aged
Prospective Studies
Retrospective Studies
V(D)J Recombination
Immunologic Deficiency Syndromes
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
[SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology
0302 clinical medicine
Receptors
Immunology and Allergy
Immunodeficiency
alpha-beta
[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology
Settore MED/38
3. Good health
[SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology
[SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology
Antigen
Immunology
[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics
Recombination-activating gene
03 medical and health sciences
medicine
[SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
Preschool
Severe combined immunodeficiency
business.industry
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology
medicine.disease
Newborn
T-Cell
Nibrin
030104 developmental biology
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics
business
Nijmegen breakage syndrome
030215 immunology
Subjects
Details
- ISSN :
- 10976825 and 00916749
- Volume :
- 143
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- The Journal of allergy and clinical immunology
- Accession number :
- edsair.doi.dedup.....73a68f29311c5c040b29428e5181f666