Zrzavy Tobias, Rieder Kerstin, Wuketich Viktoria, Thalhammer Renate, Haslacher Helmuth, Altmann Patrick, Kornek Barbara, Krajnc Nik, Monschein Tobias, Schmied Christiane, Zebenholzer Karin, Zulehner Gudrun, Berger Thomas, Rommer Paulus, Leutmezer Fritz, Bsteh Gabriel
Department of Neurology, Medical University of Vienna, Vienna, Austria.
Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria.
Front Neurol. 2024 Apr 16;15:1388941. doi: 10.3389/fneur.2024.1388941. eCollection 2024.
Recent studies proposed cellular immunoprofiling as a surrogate for predicting treatment response and/or stratifying the occurrence of adverse events (AEs) in persons with multiple sclerosis (pwMS). However, applicability in real-world circumstances is not sufficiently addressed.
We aimed to explore whether standard routine clinical leukocyte phenotyping before treatment initiation could help stratify patients according to treatment response or AEs in a real-world MS cohort.
In this retrospective study, 150 pwMS were included, who had been newly initiated on a disease-modifying drug (DMD) and had been assessed for standard immunophenotyping before DMD initiation (baseline) and at least once during the following year. Multivariate models were used to assess an association of immune subsets and the association between immune cell profiles regarding treatment response and AEs.
We found that the composition of T cell subsets was associated with relapse activity, as an increased proportion of CD8 lymphocytes at baseline indicated a higher likelihood of subsequent relapse (about 9% per 1% increase in CD8+ proportion of all CD3+ cells). This was particularly driven by patients receiving anti-CD20 therapy, where also EDSS worsening was associated with a higher number of CD8+ cells at baseline (3% increase per 10 cells). In the overall cohort, an increase in the proportion of NK cells was associated with a higher risk of EDSS worsening (5% per 1% increase). Occurrence of AEs was associated with a higher percentage of T cells and a lower number of percentual NKT cells at baseline.
Immune cell profiles are associated with treatment response and the occurrence of AEs in pwMS. Hence, immunophenotyping may serve as a valuable biomarker to enable individually tailored treatment strategies in pwMS.
近期研究提出，细胞免疫分析可作为预测多发性硬化症患者（pwMS）治疗反应和/或分层不良事件（AE）发生情况的替代指标。然而，其在现实环境中的适用性尚未得到充分探讨。
我们旨在探讨治疗开始前的标准常规临床白细胞表型分析是否有助于在真实世界的MS队列中根据治疗反应或AE对患者进行分层。
在这项回顾性研究中，纳入了150例pwMS患者，他们新开始使用疾病修饰药物（DMD），并在DMD开始前（基线）以及随后一年中至少进行了一次标准免疫表型分析。使用多变量模型评估免疫亚群的关联以及免疫细胞谱与治疗反应和AE之间的关联。
我们发现T细胞亚群的组成与复发活动相关，基线时CD8淋巴细胞比例增加表明随后复发的可能性更高（所有CD3 +细胞中CD8 +比例每增加1％，复发可能性约增加9％）。接受抗CD20治疗的患者尤其如此，其中EDSS恶化也与基线时较高数量的CD8 +细胞相关（每10个细胞增加3％）。在整个队列中，NK细胞比例增加与EDSS恶化风险较高相关（每增加1％，风险增加5％）。AE的发生与基线时较高百分比的T细胞和较低百分比的NKT细胞数量相关。
免疫细胞谱与pwMS的治疗反应和AE发生相关。因此，免疫表型分析可作为一种有价值的生物标志物，以实现pwMS患者的个体化治疗策略。
