时间标签：数据日期 2026-10-31 · 生成时间 2026-11-01 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/10/28–2026/10/31 ｜ 情报发生日期 2026-10-31
研究问题
Nonetheless, the genetic architecture underlying both susceptibility and severity remains incompletely understood.
方法
We retrospectively selected the discovery cohort from individuals diagnosed with MS or clinically isolated syndrome (CIS) according to the 2017 revisions of the McDonald criteria at the TUM University Hospital Neurology Department between 2008 and 2021, with available genotyping data and CSF leukocyte flow cytometry data.；To assess the potential impact of immunomodulatory treatment, we additionally performed an analysis restricted to individuals within the discovery cohort who had not received disease-modifying therapy at the time of CSF sampling.；We further selected a replication cohort consisting of 38 individuals with MS or CIS who had available CSF flow cytometry data collected between 2019 and 2023.；Because genotyping data were unavailable for most of these individuals, we performed genotyping specifically for this study.
核心结论
The discovery cohort consisted of 456 individuals including 410 individuals with relapsing-remitting MS (RRMS) or clinically isolated syndrome (CIS), 16 individuals with primary progressive MS (PPMS), and 30 individuals with secondary progressive MS (SPMS) ().；The median CSF NKT cell frequency in the discovery cohort was 0.7%, significantly lower than in the control cohort (median 1.5%; Wilcoxon rank-sum test p = 4.25 × 10−30).；Both the age at lumbar puncture (Pearson r = 0.13, p = 6.03 × 10−3) as well as the CSF leukocyte count (Pearson r = −0.15, p = 1.54 × 10−3) at lumbar puncture were associated with CSF NKT cell frequencies in the discovery cohort. ‖ 结论：More broadly, our results underscore the value of leveraging genetic stratification to better understand interindividual differences in immune architecture and clinical phenotype.
局限
Several limitations warrant consideration.；Second, our flow cytometric definition of NKT cells as CD3+CD56+ may include small proportions of other invariant T-cell subsets potentially introducing some heterogeneity.；In addition, although our sensitivity analysis on untreated individuals supported the primary finding, we cannot exclude an effect of disease-modifying therapies, as too few individuals received any single therapy to formally test for such effects.
对本项目的价值
★☆☆☆☆ 炎症衰老是几乎所有慢性老年病的公共通路，也是最有希望做「抗炎但保留免疫」解耦的靶点。设计 Mendelian randomization。
全文来源
PMC JATS 全文（正文 28,906 字符，已过标题/DOI 逐字归属校验）
原文题录
- 英文标题：Genetic Variation Underlying CSF Natural Killer T-Cell Frequency in Inflammatory CNS Diseases: A Genome-Wide Association Study.
- 期刊与标识：Neurol Neuroimmunol Neuroinflamm · PMID 42956320 · DOI 10.1212/nxi.0000000000200676
A 级证据分级：A 级（同行评议人体研究）
本文属人体研究证据，但需注意：观察性或小样本干预的结论不等于已证实临床获益；效应量与长期安全性仍需更大规模、更长随访的试验验证。
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