Effects of Vitamin D and Dexamethasone on Lymphocyte Proportions and Their Associations With Serum Concentrations of 25-Hydroxyvitamin D(3)In Vitro in Patients With Multiple Sclerosis or Neuromyelitis Optica Spectrum Disorder

维生素D和地塞米松对多发性硬化症或视神经脊髓炎谱系障碍患者淋巴细胞比例的影响及其与血清25-羟基维生素D3浓度的体外相关性研究

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Abstract

BACKGROUND: Clear associations have been found between vitamin D deficiency and several autoimmune diseases including multiple sclerosis (MS). However, the benefits of vitamin D supplementation on disease management remain a matter of debate. OBJECTIVE AND METHODS: Patients with MS (N=12) and neuromyelitis optica spectrum disorder (NMOSD; N=12) were enrolled along with 15 healthy controls. Changes in lymphocyte subset proportions during stimulation of their peripheral blood mononuclear cells (PBMCs) with the active form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), and correlations with serum concentrations of the vitamin D precursor 25-hydroxyvitamin D(3) (serum 25(OH)D(3)) were explored. The impact of 1,25(OH)(2)D(3) stimulation on the expression of vitamin-D-responsive genes in immune cells was also investigated. RESULTS: In both MS and NMOSD, stimulation of PBMCs with 1,25(OH)(2)D(3) followed by steroid suppressed the proliferation of total lymphocytes and T cells. The ratio of CD19(+)CD27(+) memory B cells (Bmem) to all B cells after stimulation with 1,25(OH)(2)D(3) was negatively correlated with serum 25(OH)D(3) in MS (Spearman's ρ=-0.594, p=0.042), but positively correlated in NMOSD (Pearson's r = 0.739, p=0.006). However, there was no relationship between the ratio of Bmem to CD19(+)CD24(+)CD38(+) regulatory B cells and serum 25(OH)D(3) in either MS or NMOSD. In addition, the level of 1,25(OH)(2)D(3)-induced CYP24A1 mRNA expression in PBMCs was significantly and negatively correlated with serum 25(OH)D(3) (for ΔC(T), r=0.744, p=0.014) in MS. CONCLUSION: These findings suggest a beneficial impact of stimulation of PBMCs with vitamin D followed by steroid on the T-cell population. The association between patient serum 25(OH)D(3) and the proportion of Bmem under immune-cell stimulation differed between MS and NMOSD. Further investigations are warranted with larger patient populations.

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