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The TCR Repertoire Reconstitution in Multiple Sclerosis: Comparing One-Shot and Continuous Immunosuppressive Therapies
- Source :
- Frontiers in Immunology, Frontiers in Immunology, Vol 11 (2020)
- Publication Year :
- 2019
-
Abstract
- Natalizumab (NTZ) and autologous hematopoietic stem cell transplantation (AHSCT) are two successful treatments for relapsing-remitting multiple sclerosis (RRMS), an autoimmune T-cell-driven disorder affecting the central nervous system that is characterized by relapses interspersed with periods of complete or partial recovery. Both RRMS treatments have been documented to impact T-cell subpopulations and the T-cell receptor (TCR) repertoire in terms of clone frequency, but, so far, the link between T-cell naive and memory populations, autoimmunity, and treatment outcome has not yet been established hindering insight into the post-treatment TCR landscape of MS patients. To address this important knowledge gap, we tracked peripheral T-cell subpopulations (naïve and memory CD4+ and CD8+) across 15 RRMS patients before and after two years of continuous treatment (NTZ) and a single treatment course (AHSCT) by high-throughput TCRß sequencing. We found that the two MS treatments left treatment-specific multidimensional traces in patient TCRß repertoire dynamics with respect to clonal expansion, clonal diversity and repertoire architecture. Comparing MS TCR sequences with published datasets suggested that the majority of public TCRs belonged to virus-associated sequences. In summary, applying multi-dimensional computational immunology to a TCRß dataset of treated MS patients, we show that qualitative changes of TCRß repertoires encode treatment-specific information that may be relevant for future clinical trials monitoring and personalized MS follow-up, diagnosis and treatment regimes. Natalizumab (NTZ) and autologous hematopoietic stem cell transplantation (AHSCT) are two successful treatments for relapsing–remitting multiple sclerosis (RRMS), an autoimmune T-cell–driven disorder affecting the central nervous system that is characterized by relapses interspersed with periods of complete or partial recovery. Both RRMS treatments have been documented to impact T-cell subpopulations and the T-cell receptor (TCR) repertoire in terms of clone frequency, but, so far, the link between T-cell naive and memory populations, autoimmunity, and treatment outcome has not yet been established hindering insight into the posttreatment TCR landscape of MS patients. To address this important knowledge gap, we tracked peripheral T-cell subpopulations (naive and memory CD4+ and CD8+) across 15 RRMS patients before and after 2 years of continuous treatment (NTZ) and a single treatment course (AHSCT) by high-throughput TCRβ sequencing. We found that the two MS treatments left treatment-specific multidimensional traces in patient TCRβ repertoire dynamics with respect to clonal expansion, clonal diversity, and repertoire architecture. Comparing MS TCR sequences with published datasets suggested that the majority of public TCRs belonged to virus-associated sequences. In summary, applying multidimensional computational immunology to a TCRβ dataset of treated MS patients, we show that qualitative changes of TCRβ repertoires encode treatment-specific information that may be relevant for future clinical trials monitoring and personalized MS follow-up, diagnosis, and treatment regimens.
- Subjects :
- 0301 basic medicine
lcsh:Immunologic diseases. Allergy
Adult
CD4-Positive T-Lymphocytes
Male
medicine.medical_treatment
system immunology, T cell subpopulations, T cell repertoire diversity, multiple sclerosis, disease modifying therapies
Receptors, Antigen, T-Cell, alpha-beta
Immunology
Clone (cell biology)
Hematopoietic stem cell transplantation
Biology
CD8-Positive T-Lymphocytes
multiple sclerosis
Transplantation, Autologous
03 medical and health sciences
0302 clinical medicine
Natalizumab
Multiple Sclerosis, Relapsing-Remitting
medicine
Immunology and Allergy
Humans
Immunologic Factors
disease-modifying therapies
Original Research
Immunosuppression Therapy
system immunology
Repertoire
Multiple sclerosis
T-cell repertoire diversity
T-cell receptor
Hematopoietic Stem Cell Transplantation
Middle Aged
medicine.disease
3. Good health
030104 developmental biology
Computational immunology
Female
T-cell subpopulations
lcsh:RC581-607
CD8
030215 immunology
medicine.drug
Subjects
Details
- ISSN :
- 16643224
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Frontiers in immunology
- Accession number :
- edsair.doi.dedup.....8d90103127458c208d8e33aac251ff8a