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November 2021; 8 (6) ArticleOpen Access

Melanoma Cell Adhesion Molecule Expressing Helper T Cells in CNS Inflammatory Demyelinating Diseases

Ryotaro Ikeguchi, Yuko Shimizu, Akihiro Kondo, Natsuki Kanda, Hayato So, Haruka Kojima, Kazuo Kitagawa
First published August 24, 2021, DOI: https://doi.org/10.1212/NXI.0000000000001069
Ryotaro Ikeguchi
From the Department of Neurology, Tokyo Women's Medical University, Japan.
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  • For correspondence: ikeguchi.ryotaro@twmu.ac.jp
Yuko Shimizu
From the Department of Neurology, Tokyo Women's Medical University, Japan.
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Akihiro Kondo
From the Department of Neurology, Tokyo Women's Medical University, Japan.
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  • For correspondence: akihiro19880901@gmail.com
Natsuki Kanda
From the Department of Neurology, Tokyo Women's Medical University, Japan.
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  • For correspondence: benjavinci.again12@gmail.com
Hayato So
From the Department of Neurology, Tokyo Women's Medical University, Japan.
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  • For correspondence: beruguso@gmail.com
Haruka Kojima
From the Department of Neurology, Tokyo Women's Medical University, Japan.
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  • For correspondence: ryuuya5555@yahoo.co.jp
Kazuo Kitagawa
From the Department of Neurology, Tokyo Women's Medical University, Japan.
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  • For correspondence: kitagawa.kazuo@twmu.ac.jp
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Melanoma Cell Adhesion Molecule Expressing Helper T Cells in CNS Inflammatory Demyelinating Diseases
Ryotaro Ikeguchi, Yuko Shimizu, Akihiro Kondo, Natsuki Kanda, Hayato So, Haruka Kojima, Kazuo Kitagawa
Neurol Neuroimmunol Neuroinflamm Nov 2021, 8 (6) e1069; DOI: 10.1212/NXI.0000000000001069

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    Figure 1 Frequency and Absolute Number of MCAM+ mTh Cells Increased in Patients With NMOSD

    (A.a–A.c) Representative dot plot and histogram of MCAM+ (CD146+) mTh cells (CD3+ CD4+ CD45RA− lymphocytes) using flow cytometry. The lymphocyte subsets included mTh cells, CD3+ CD4+ CD45RA− lymphocytes; naive helper T cells, CD3+ CD4+ CD45RA+ lymphocytes; CD8+ T cells, CD3+ CD8+ lymphocytes; and B cells, CD3− CD19+ lymphocytes. The MCAM+ (CD146+) and α4-integrin+ (CD49d+) populations were defined based on the fluorescence intensity of the isotype control. (B) Frequency of MCAM+ cells in all lymphocyte subsets (n = 183: 72 patients with MS, 29 with NMOSD, 23 with MG, 34 with NIND, and 25 HCs). (C.a–C.d) Frequency of MCAM+ cells in all participants (72 patients with MS, 29 with NMOSD, 23 with MG, 34 with NIND, and 25 HCs). (D.a–D.c) Absolute number of MCAM+ cells in all patients (40 patients with MS, 23 with NMOSD, 17 with MG, and 26 NIND). Dimethyl fumarate (DMF)- (n = 11) and fingolimod- (n = 18) treated patients with MS were excluded because treatment with these DMDs reduces the absolute number of lymphocytes. Dots represent individual samples. The lower, upper, and middle lines correspond to the 25th centile, 75th centile, and median, respectively. *p < 0.05, **p < 0.01, and ***p < 0.001. HC = healthy control; MCAM = melanoma cell adhesion molecule; MG = myasthenia gravis; mTh cell = memory helper T cell; NIND = noninflammatory neurologic disorders; NMOSD = neuromyelitis optica spectrum disorder; ns = not significant.

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    Figure 2 Frequency and Absolute Number of MCAM+ Lymphocytes in DMD- or Steroid-Treated Patients With CNS IDD

    (A.a–A.c) Frequency of MCAM+ cells in each lymphocyte subset among the DMD- or steroid-treated patients with MS (IFN-β [n = 12], DMF [n = 11], FTY [n = 18], and NTZ [n = 6]) and untreated patients with MS (n = 25). (B.a–B.c) Absolute number of MCAM+ cells in each lymphocyte subset among the DMD- or steroid-treated patients with MS (IFN-β [n = 9], DMF [n = 10], FTY [n = 18], and NTZ [n = 6]) and untreated patients (n = 24). (C) Frequency of MCAM+ mTh cells in the PB of patients with NMOSD and MG treated with or without PSL. At the time of examination, 25 of the 29 patients with NMOSD and 19 of the 23 patients with MG were undergoing treatment with oral PSL. Dots represent individual samples. The lower, upper, and middle lines correspond to the 25th centile, 75th centile, and median, respectively. *p < 0.05, **p < 0.01, and ***p < 0.001. DMD = disease-modifying drug; DMF = dimethyl fumarate; FTY = fingolimod; IDD = inflammatory demyelinating disease; IFN = interferon; MCAM = melanoma cell adhesion molecule; MG = myasthenia gravis; mTh cell = memory helper T cell; NMOSD = neuromyelitis optica spectrum disorder; ns = not significant; NTZ = natalizumab; PB = peripheral blood; PSL = prednisolone.

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    Figure 3 Frequency of MCAM+ mTh Cells Was Increased in the CSF of Patients With CNS IDD

    (A.a–A.c) Frequency of CSF and PB MCAM+ lymphocytes (MS [n = 10], NMOSD [n = 6], and NIND [n = 15]). At examination, 8 patients with MS and 4 patients with NMOSD were in the relapse phase. (B.a–B.b) Absolute number of CSF MCAM+ lymphocytes (MS [n = 10], NMOSD [n = 5], and NIND [n = 13]). The absolute number of MCAM+ B cells is not shown in this figure because this subset has been rarely observed in the CSF. Closed circles represent the relapse phase, and closed squares represent the remission phase in (A) and (B). (C) Correlation between the frequencies of PB and CSF MCAM+ mTh cells in patients with (C.a) NMOSD (n = 6, closed square) and NIND (n = 15, closed triangle) and (C.b) only in patients with MS (n = 10, closed circle). Dots represent individual samples. The lower, upper, and middle lines correspond to the 25th centile, 75th centile, and median, respectively. *p < 0.05, **p < 0.01, and ***p < 0.001. IDD = inflammatory demyelinating disease; MCAM = melanoma cell adhesion molecule; mTh cell = memory helper T cell; NIND = noninflammatory neurologic disorders; NMOSD = neuromyelitis optica spectrum disorder; ns = not significant; PB = peripheral blood.

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