To elucidate relationships between melanoma cell adhesion molecule (MCAM) expression in lymphocyte subsets and the pathogenesis of CNS-demyelinating diseases. 

Adhesion molecules expressed on lymphocytes are closely related to the pathogenesis of CNS-demyelinating diseases. Recently, among adhesion molecules, the pathogenicity of MCAM+ helper T (Th) cells is considered in multiple sclerosis (MS).

Fifty-eight patients with MS, 22 with neuromyelitis spectrum disorder (NMOSD), 33 with non-inflammatory neurological disorders (NINDs), and 26 healthy controls (HCs) were enrolled. We analyzed the frequencies of MCAM+ memory Th cells (mTh), naïve Th cells, CD8+ T cells, and B cells in peripheral blood by flow cytometry. We compared the frequencies and absolute numbers of MCAM+ lymphocytes between each disease. We analyzed the influence of disease-modifying drugs (DMDs) or steroid on MCAM expression. The relationships between MCAM expression and clinical parameters as well as the frequency of regulatory T cells (Tregs) were examined. 

The frequency of MCAM expression was significantly higher in mTh subset than in other subsets. The frequency of MCAM+ mTh was significantly higher in patients with NMOSD than in those with MS, and NINDs, or HCs. The absolute numbers of MCAM+ mTh in MS patients treated with fingolimod were significantly lower than those in MS patients treated with IFNβ, steroid, or without immunotherapy. No correlation was observed between MCAM expression and clinical parameters or the frequency of Tregs. Frequency of Treg was significantly higher in MS patients treated with fingolimod than in patients with IFNβ, steroid, or without immunotherapy.

Our results indicate the involvement of MCAM even in pathogenesis of NMOSD. Fingolimod decreases mTh in peripheral blood including pathogenic MCAM+ mTh in MS. MCAM may be a therapeutic target of CNS demyelinating diseases. Further study is needed to elucidate detailed pathogenesis of MCAM in MS and NMOSD.