Alemtuzumab in Multiple Sclerosis: Short- and Long-Term Effects of Immunodepletion on the Peripheral Treg Compartment.
Adolescent
Adult
Alemtuzumab
/ pharmacology
Antineoplastic Agents, Immunological
/ pharmacology
Biomarkers
CD4 Lymphocyte Count
Cytotoxicity, Immunologic
Female
Humans
Immunologic Memory
/ drug effects
Immunomodulation
/ drug effects
Immunophenotyping
Lymphocyte Depletion
Male
Middle Aged
Multiple Sclerosis
/ drug therapy
Receptors, Antigen, T-Cell
/ metabolism
T-Lymphocytes, Regulatory
/ immunology
Treatment Outcome
Young Adult
alemtuzumab
human
immunodepletion
multiple sclerosis
regulatory t cells
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2019
2019
Historique:
received:
19
12
2018
accepted:
13
05
2019
entrez:
20
6
2019
pubmed:
20
6
2019
medline:
29
10
2020
Statut:
epublish
Résumé
Treatment with alemtuzumab is followed by an early increase in Treg frequencies. Whether naïve and memory subsets are differentially affected and how depletion influences dysfunctional MS-Treg is unclear. In this study, we analyzed the effect of alemtuzumab on regulatory T-cells (Treg) in patients with multiple sclerosis (MS). For this purpose 182 blood samples from 25 MS patients were taken shortly before treatment and serially for up to 24 months after two alemtuzumab cycles. We studied Treg by flow cytometry (quantitation, phenotypical characterization), real-time polymerase chain reaction (T-cell receptor (TCR) excision circles [TREC] content), CDR3-spectratyping (clonal distribution), and proliferation assays (suppressive function). CD52-mediated cytolysis of Treg and conventional T-cells was determined by a complement-dependent cytolysis assay. Our studies revealed that 1 week post-alemtuzumab, Treg were depicted at constant frequencies among CD4
Identifiants
pubmed: 31214176
doi: 10.3389/fimmu.2019.01204
pmc: PMC6558003
doi:
Substances chimiques
Antineoplastic Agents, Immunological
0
Biomarkers
0
Receptors, Antigen, T-Cell
0
Alemtuzumab
3A189DH42V
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1204Références
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