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Immune Reconstitution Following Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis: A Review on Behalf of the EBMT Autoimmune Diseases Working Party

Multiple sclerosis (MS) is a central nervous system (CNS) disorder, which is mediated by an abnormal immune response coordinated by T and B cells resulting in areas of inflammation, demyelination, and axonal loss. Disease-modifying treatments (DMTs) are available to dampen the inflammatory aggressio...

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Autores principales: Cencioni, Maria Teresa, Genchi, Angela, Brittain, Gavin, de Silva, Thushan I., Sharrack, Basil, Snowden, John Andrew, Alexander, Tobias, Greco, Raffaella, Muraro, Paolo A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8846289/
https://www.ncbi.nlm.nih.gov/pubmed/35178046
http://dx.doi.org/10.3389/fimmu.2021.813957
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author Cencioni, Maria Teresa
Genchi, Angela
Brittain, Gavin
de Silva, Thushan I.
Sharrack, Basil
Snowden, John Andrew
Alexander, Tobias
Greco, Raffaella
Muraro, Paolo A.
author_facet Cencioni, Maria Teresa
Genchi, Angela
Brittain, Gavin
de Silva, Thushan I.
Sharrack, Basil
Snowden, John Andrew
Alexander, Tobias
Greco, Raffaella
Muraro, Paolo A.
author_sort Cencioni, Maria Teresa
collection PubMed
description Multiple sclerosis (MS) is a central nervous system (CNS) disorder, which is mediated by an abnormal immune response coordinated by T and B cells resulting in areas of inflammation, demyelination, and axonal loss. Disease-modifying treatments (DMTs) are available to dampen the inflammatory aggression but are ineffective in many patients. Autologous hematopoietic stem cell transplantation (HSCT) has been used as treatment in patients with a highly active disease, achieving a long-term clinical remission in most. The rationale of the intervention is to eradicate inflammatory autoreactive cells with lympho-ablative regimens and restore immune tolerance. Immunological studies have demonstrated that autologous HSCT induces a renewal of TCR repertoires, resurgence of immune regulatory cells, and depletion of proinflammatory T cell subsets, suggesting a “resetting” of immunological memory. Although our understanding of the clinical and immunological effects of autologous HSCT has progressed, further work is required to characterize the mechanisms that underlie treatment efficacy. Considering that memory B cells are disease-promoting and stem-like T cells are multipotent progenitors involved in self-regeneration of central and effector memory cells, investigating the reconstitution of B cell compartment and stem and effector subsets of immunological memory following autologous HSCT could elucidate those mechanisms. Since all subjects need to be optimally protected from vaccine-preventable diseases (including COVID-19), there is a need to ensure that vaccination in subjects undergoing HSCT is effective and safe. Additionally, the study of vaccination in HSCT-treated subjects as a means of evaluating immune responses could further distinguish broad immunosuppression from immune resetting.
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spelling pubmed-88462892022-02-16 Immune Reconstitution Following Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis: A Review on Behalf of the EBMT Autoimmune Diseases Working Party Cencioni, Maria Teresa Genchi, Angela Brittain, Gavin de Silva, Thushan I. Sharrack, Basil Snowden, John Andrew Alexander, Tobias Greco, Raffaella Muraro, Paolo A. Front Immunol Immunology Multiple sclerosis (MS) is a central nervous system (CNS) disorder, which is mediated by an abnormal immune response coordinated by T and B cells resulting in areas of inflammation, demyelination, and axonal loss. Disease-modifying treatments (DMTs) are available to dampen the inflammatory aggression but are ineffective in many patients. Autologous hematopoietic stem cell transplantation (HSCT) has been used as treatment in patients with a highly active disease, achieving a long-term clinical remission in most. The rationale of the intervention is to eradicate inflammatory autoreactive cells with lympho-ablative regimens and restore immune tolerance. Immunological studies have demonstrated that autologous HSCT induces a renewal of TCR repertoires, resurgence of immune regulatory cells, and depletion of proinflammatory T cell subsets, suggesting a “resetting” of immunological memory. Although our understanding of the clinical and immunological effects of autologous HSCT has progressed, further work is required to characterize the mechanisms that underlie treatment efficacy. Considering that memory B cells are disease-promoting and stem-like T cells are multipotent progenitors involved in self-regeneration of central and effector memory cells, investigating the reconstitution of B cell compartment and stem and effector subsets of immunological memory following autologous HSCT could elucidate those mechanisms. Since all subjects need to be optimally protected from vaccine-preventable diseases (including COVID-19), there is a need to ensure that vaccination in subjects undergoing HSCT is effective and safe. Additionally, the study of vaccination in HSCT-treated subjects as a means of evaluating immune responses could further distinguish broad immunosuppression from immune resetting. Frontiers Media S.A. 2022-02-01 /pmc/articles/PMC8846289/ /pubmed/35178046 http://dx.doi.org/10.3389/fimmu.2021.813957 Text en Copyright © 2022 Cencioni, Genchi, Brittain, de Silva, Sharrack, Snowden, Alexander, Greco and Muraro https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Cencioni, Maria Teresa
Genchi, Angela
Brittain, Gavin
de Silva, Thushan I.
Sharrack, Basil
Snowden, John Andrew
Alexander, Tobias
Greco, Raffaella
Muraro, Paolo A.
Immune Reconstitution Following Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis: A Review on Behalf of the EBMT Autoimmune Diseases Working Party
title Immune Reconstitution Following Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis: A Review on Behalf of the EBMT Autoimmune Diseases Working Party
title_full Immune Reconstitution Following Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis: A Review on Behalf of the EBMT Autoimmune Diseases Working Party
title_fullStr Immune Reconstitution Following Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis: A Review on Behalf of the EBMT Autoimmune Diseases Working Party
title_full_unstemmed Immune Reconstitution Following Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis: A Review on Behalf of the EBMT Autoimmune Diseases Working Party
title_short Immune Reconstitution Following Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis: A Review on Behalf of the EBMT Autoimmune Diseases Working Party
title_sort immune reconstitution following autologous hematopoietic stem cell transplantation for multiple sclerosis: a review on behalf of the ebmt autoimmune diseases working party
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8846289/
https://www.ncbi.nlm.nih.gov/pubmed/35178046
http://dx.doi.org/10.3389/fimmu.2021.813957
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