Poor T-cell receptor β repertoire diversity early posttransplant for severe combined immunodeficiency predicts failure of immune reconstitution
| Autor: | Ewelina Mamcarz, Stephen R. Daley, Blachy J. Dávila Saldaña, Jennifer M. Puck, Jason Yu, Christopher C. Dvorak, Riccardo Castagnoli, Catherine K. Chang, Ottavia M. Delmonte, Luigi D. Notarangelo, Suk See De Ravin, Morton J. Cowan, Linda M. Griffith |
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| Rok vydání: | 2021 |
| Předmět: |
Severe combined immunodeficiency
DCLRE1C Repertoire Genetic enhancement Receptors Antigen T-Cell alpha-beta Immunology T-cell receptor Hematopoietic Stem Cell Transplantation Receptors Antigen T-Cell Infant respiratory system Biology medicine.disease Complementarity Determining Regions Transplantation Immune system Immune Reconstitution medicine Immunology and Allergy Humans Severe Combined Immunodeficiency Receptor human activities |
| Zdroj: | The Journal of allergy and clinical immunology. 149(3) |
| ISSN: | 1097-6825 |
| Popis: | Background Development of a diverse T-cell receptor β (TRB) repertoire is associated with immune recovery following hematopoietic cell transplantation (HCT) for severe combined immunodeficiency (SCID). High-throughput sequencing of the TRB repertoire allows evaluation of clonotype dynamics during immune reconstitution. Objectives We investigated whether longitudinal analysis of the TRB repertoire would accurately describe T-cell receptor diversity and illustrate the quality of T-cell reconstitution following HCT or gene therapy for SCID. Methods We used high-throughput sequencing to study composition and diversity of the TRB repertoire in 27 infants with SCID at 3, 6, and 12 months and yearly posttreatment(s). Total RNA from peripheral blood was used as template to amplify TRB rearrangements. Results TRB sequence analysis showed poor diversity at 3 months, followed by significant improvement by 6 months after cellular therapies. Kinetics of development of TRB diversity were similar in patients with a range of underlying gene defects. However, in patients with RAG and DCLRE1C defects, HCT with no conditioning or immune suppression only resulted in lower diversity than did HCT with conditioning. HCT from a matched donor correlated with higher diversity than did HCT from a mismatched donor. Naive CD4+ T-cell count at 6 months post-HCT correlated with higher TRB diversity. A Shannon index of diversity of 5.2 or lower 3 months after HCT predicted a need for a second intervention. Conclusions TRB repertoire after hematopoietic cell therapies for SCID provides a quantitative and qualitative measure of diversity of T-cell reconstitution and permits early identification of patients who may require a second intervention. |
| Databáze: | OpenAIRE |
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