背景:循环免疫细胞在多发性硬化症(MS)中起致病作用。然而,特定淋巴细胞亚群的作用还没有公布,尤其是在进步阶段。我们旨在研究辛波莫德治疗活动性继发性进展性MS(aSPMS)期间的淋巴细胞变化及其与临床结果的关系。
方法:我们招募了46名aSPMS患者,开始接受西波莫德治疗,在预定的时间范围内进行至少6个月的随访和两次访问,以及14名性别和年龄匹配的健康对照(HCs)。基线时回顾性收集临床和实验室数据,3rd,6th,12th,MS患者为24个月,和基线时的HC。
结果:在基线时,SPMS患者的初始调节性T淋巴细胞(p=0.02)与HCS。随着时间的推移,SPMS患者显示CD4+T降低(coeff。范围=-24/-17,95%CI范围=-31.60至-10.40),B淋巴细胞(coeff。范围=-3.77/-2.54,95%CI范围=-6.02至-0.35),记忆调节B细胞(coeff。范围=-0.78/-0.57,95%CI范围=-1.24至-0.17)和CD4/CD8比率(系数。范围=-4.44/-0.67,95%CI范围=-1.61至-0.17)自此后第3个月起与基线,并从12个月开始减少CD3+CD20+淋巴细胞(coeff。范围=-0.32/-0.24,95%CI范围=-0.59至-0.03)。从第3个月起,接受辛波莫德治疗时没有出现残疾进展的患者显示B淋巴细胞减少(coeff。范围=-4.23/-2.32,95%CI范围=-7.53至-0.15),从12个月起CD3+CD20+淋巴细胞减少(系数。范围=-0.32/-0.24,95%CI范围=-0.59至-0.03)与患者经历进展。
结论:使用西波莫德治疗的患者显示T淋巴细胞和B淋巴细胞减少,尤其是CD4+,CD3+CD20+和初始调节性T细胞和记忆调节性B细胞。使用辛波莫德治疗时的残疾进展与对B和CD3CD20淋巴细胞的不太明显的影响有关。
BACKGROUND: Circulating immune cells play a pathogenic role in multiple sclerosis (MS). However, the role of specific lymphocyte subpopulations is not unveiled yet, especially in progressive stages. We aimed to investigate lymphocyte changes during
siponimod treatment in active secondary progressive MS (aSPMS) and their associations with clinical outcomes.
METHODS: We enrolled 46 aSPMS patients starting on
siponimod treatment with at least 6 months of follow-up and two visits within the scheduled timeframes and 14 sex- and age-matched healthy controls (HCs). Clinical and laboratory data were collected retrospectively at baseline, 3rd, 6th, 12th, and 24th month for MS patients, and at baseline for HCs.
RESULTS: At baseline SPMS patients presented with increased naïve regulatory T lymphocytes (p = 0.02) vs. HCs. Over time, SPMS patients showed decreased T CD4+ (coeff. range = -24/-17, 95% CI range = -31.60 to -10.40), B lymphocyte (coeff. range = -3.77/-2.54, 95% CI range = -6.02 to -0.35), memory regulatory B cells (coeff. range = -0.78/-0.57, 95% CI range = -1.24 to -0.17) and CD4/CD8 ratio (coeff. range = -4.44/-0.67, 95% CI range = -1.61 to -0.17) from month 3 thereafter vs. baseline, and reduced CD3+CD20+ lymphocytes from month 12 thereafter (coeff. range = -0.32/-0.24, 95% CI range = -0.59 to -0.03). Patients not experiencing disability progression while on
siponimod treatment showed B lymphocyte reduction from month 3 (coeff. range = -4.23/-2.32, 95% CI range = -7.53 to -0.15) and CD3+CD20+ lymphocyte reduction from month 12 (coeff. range = -0.32/-0.24, 95% CI range = -0.59 to -0.03) vs. patients experiencing progression.
CONCLUSIONS: Patients treated with
siponimod showed a T and B lymphocyte reduction, especially CD4+, CD3+CD20+ and naïve regulatory T cells and memory regulatory B cells. Disability progression while on
siponimod treatment was associated with a less pronounced effect on B and CD3+CD20+ lymphocytes.