Abstract
Background and Objective To elucidate the relationship between melanoma cell adhesion molecule (MCAM)-expressing lymphocytes and pathogenesis of CNS inflammatory demyelinating diseases (IDDs).
Methods Patients with multiple sclerosis (MS) (n = 72) and neuromyelitis optica spectrum disorder (NMOSD, n = 29) were included. We analyzed the frequency and absolute numbers of MCAM+ lymphocytes (memory helper T [mTh] cells, naive helper T cells, CD8+ T cells, and B cells) in the peripheral blood (PB) and the CSF of patients with MS and NMOSD, treated with/without disease-modifying drugs (DMDs) or steroids, using flow cytometry.
Results The frequency of MCAM+ cells was higher in the mTh cell subset than that in other lymphocyte subsets. A significant increase in the frequency and the absolute number of MCAM+ mTh cells was observed in the PB of patients with NMOSD, whereas no increase was observed in the PB of patients with MS. The frequency of CSF MCAM+ mTh cells was higher in relapsing patients with MS and NMOSD than that in the control group. Although there was no difference in the frequencies of MCAM+ lymphocytes among the DMD-treated groups, fingolimod decreased the absolute number of MCAM+ lymphocytes.
Discussion MCAM+ mTh cells were elevated in the CSF of relapsing patients with MS and in both the PB and CSF of patients with NMOSD. These results indicate that MCAM contributes to the pathogenesis of MS and NMOSD through different mechanisms. MCAM could be a therapeutic target of CNS IDDs, and further study is needed to elucidate the underlying mechanism of MCAM in CNS IDD pathogenesis.
Glossary
- ANOVA=
- analysis of variance;
- DMD=
- disease-modifying drug;
- DMF=
- dimethyl fumarate;
- EAE=
- experimental autoimmune encephalomyelitis;
- EDSS=
- Expanded Disability Status Scale;
- FTY=
- fingolimod;
- HC=
- healthy control;
- IDD=
- inflammatory demyelinating disease;
- IFN=
- interferon;
- IL=
- interleukin;
- MCAM=
- melanoma cell adhesion molecule;
- MG=
- myasthenia gravis;
- mTh cell=
- memory helper T cell;
- NIND=
- noninflammatory neurologic disorder;
- NMOSD=
- neuromyelitis optica spectrum disorder;
- NTZ=
- natalizumab;
- PB=
- peripheral blood;
- PBMC=
- PB mononuclear cells;
- PSL=
- prednisolone;
- RA=
- rheumatoid arthritis;
- Th1=
- T helper 1;
- Th17=
- T helper 17
Footnotes
Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.
The Article Processing Charge was funded by the authors.
- Received February 5, 2021.
- Accepted in final form July 21, 2021.
- Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
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