Comparing the immune mechanisms and efficacy of lympho-depleting therapies in multiple sclerosis
File(s)
Accepted version
Author(s)
De Matteis, Eleonora
Martin, Roland
Muraro, Paolo
Type
Journal Article
Abstract
Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system characterized by aberrant immune responses that drive neuroinflammation and neurodegeneration. The central role of adaptive immunity in MS pathogenesis makes T and B cells key targets for
immunomodulatory and immunosuppressive therapies, including lympho-depleting therapies. Established
lympho-depleting approaches include autologous hematopoietic stem cell transplantation (AHSCT),
alemtuzumab, cladribine, and anti-CD20 monoclonal antibodies, while chimeric antigen receptor T-cell
(CAR-T) therapies targeting B cells and/or plasma cells are emerging as experimental strategies. Lymphodepleting therapies deplete T- and B-cell populations to different extents, leading to distinct quantitative and qualitative changes across the innate and adaptive immune compartments. Shared effects include suppression of pro-inflammatory immune populations and relative expansion of regulatory subsets, whereas the degree of immune renewal appears to differ across therapies. In particular, AHSCT is the only therapy associated with near-complete T and B cell repertoire renewal, but its efficacy compared with the other lympho-depleting therapies remains to be established. Ongoing head-to-head studies comparing
AHSCT with other lympho-depleting therapies are expected to clarify relative efficacy, mechanisms of
action, and immunological correlates of clinical response. The aim of this review is to summarize the available evidence on the immunological mechanisms of lympho-depleting therapies, including their qualitative and quantitative effects on the innate and adaptive immune compartments and on T- and B-cell repertoires, and to discuss how these changes might relate to the extent and durability of clinical response.
immunomodulatory and immunosuppressive therapies, including lympho-depleting therapies. Established
lympho-depleting approaches include autologous hematopoietic stem cell transplantation (AHSCT),
alemtuzumab, cladribine, and anti-CD20 monoclonal antibodies, while chimeric antigen receptor T-cell
(CAR-T) therapies targeting B cells and/or plasma cells are emerging as experimental strategies. Lymphodepleting therapies deplete T- and B-cell populations to different extents, leading to distinct quantitative and qualitative changes across the innate and adaptive immune compartments. Shared effects include suppression of pro-inflammatory immune populations and relative expansion of regulatory subsets, whereas the degree of immune renewal appears to differ across therapies. In particular, AHSCT is the only therapy associated with near-complete T and B cell repertoire renewal, but its efficacy compared with the other lympho-depleting therapies remains to be established. Ongoing head-to-head studies comparing
AHSCT with other lympho-depleting therapies are expected to clarify relative efficacy, mechanisms of
action, and immunological correlates of clinical response. The aim of this review is to summarize the available evidence on the immunological mechanisms of lympho-depleting therapies, including their qualitative and quantitative effects on the innate and adaptive immune compartments and on T- and B-cell repertoires, and to discuss how these changes might relate to the extent and durability of clinical response.
Date Acceptance
2026-09-09
Citation
Neurology: Neuroimmunology & Neuroinflammation
ISSN
2332-7812
Publisher
Wolters Kluwer
Journal / Book Title
Neurology: Neuroimmunology & Neuroinflammation
Copyright Statement
Copyright This paper is embargoed until publication. Once published the Version of Record (VoR) will be available on immediate open access.
License URL
Publication Status
Accepted