From the Department of Neurology, Tokyo Women's Medical University, Japan.
Neurol Neuroimmunol Neuroinflamm. 2021 Aug 24;8(6). doi: 10.1212/NXI.0000000000001069. Print 2021 Nov.
To elucidate the relationship between melanoma cell adhesion molecule (MCAM)-expressing lymphocytes and pathogenesis of CNS inflammatory demyelinating diseases (IDDs).
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.
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.
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.
阐明黑色素瘤细胞黏附分子（MCAM）表达的淋巴细胞与中枢神经系统炎性脱髓鞘疾病（CNS-IDDs）发病机制之间的关系。
纳入多发性硬化症（MS）患者（n=72）和视神经脊髓炎谱系障碍（NMOSD，n=29）患者。我们采用流式细胞术分析了 MS 和 NMOSD 患者外周血（PB）和脑脊液（CSF）中 MCAM 淋巴细胞（记忆辅助 T [mTh]细胞、幼稚辅助 T 细胞、CD8 T 细胞和 B 细胞）的频率和绝对数，这些患者接受了/未接受疾病修正药物（DMDs）或类固醇治疗。
MCAM 细胞在 mTh 细胞亚群中的频率高于其他淋巴细胞亚群。NMOSD 患者 PB 中 MCAM mTh 细胞的频率和绝对数显著增加，而 MS 患者 PB 中未观察到增加。复发型 MS 和 NMOSD 患者 CSF 中 MCAM mTh 细胞的频率高于对照组。尽管 DMD 治疗组之间 MCAM 淋巴细胞的频率没有差异，但芬戈莫德可降低 MCAM 淋巴细胞的绝对数。
复发型 MS 和 NMOSD 患者的 CSF 中 MCAM mTh 细胞升高，且 PB 和 CSF 中均升高。这些结果表明，MCAM 通过不同的机制参与 MS 和 NMOSD 的发病机制。MCAM 可能是 CNS-IDDs 的治疗靶点，需要进一步研究以阐明 MCAM 在 CNS-IDD 发病机制中的潜在机制。
