对多发性硬化症患者细胞特异性表观遗传年龄加速的评估
Vicki Maltby1, Alexandre Xavier1, Ewoud Ewing1
1From the School of Medicine and Public Health (V.M., R.L., J.L.-S.), University of Newcastle, University Drive, Callaghan; Immune Health Program (V.M., A.X., J.L.-S.), Hunter Medical Research Institute; Department of Neurology (V.M., J.L.-S.), John Hunter Hospital, New Lambton Heights; School of Biomedical Sciences and Pharmacy (A.X.), University of Newcastle, University Drive, Callaghan, Australia; Department of Clinical Neuroscience (E.E., L.K., M.J.), Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden; Department of Neuroscience (M.-P.C., S.S., H.B., V.J.), Central Clinical School, Monash University, Victoria; Division of Molecular Genetics (R.J.S.), Pathology North, John Hunter Hospital, New Lambton Heights; MSBase Foundation (H.B.), Melbourne, Australia; Institute of Clinical Medicine (S.B.), University of Oslo,; Department of Neurology (S.B.), Oslo University Hospital, Norway; Flinders University (M.S.), Adelaide; Menzies Institute for Medical Research (I.A.M., B.V.T.), University of Tasmania, Hobart; Florey Institute of Neuroscience and Mental Health (A.-L.P.), The University of Melbourne; Centre of Epidemiology and Biostatistics (A.-L.P.), School of Population and Global Health, University of Melbourne; Murdoch Children's Research Institute (A.-L.P.), Royal Children's Hospital, Melbourne; and Centre for Genomics and Personalized Health (R.L.), School of Biomedical Science, Queensland University of Technology, Kelvin Grove, Australia.
免疫细胞,特别是B细胞的加速衰老与多发性硬化症 (MS) 有关. 这种B细胞的表观遗传年龄加速表明,在MS的发展和进展中,过早的免疫衰老起着作用.
科学领域:
- 免疫学 免疫学 免疫学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 老年学是一门学科.
背景情况:
- 加快免疫系统衰老 (免疫衰老) 可能会影响多发性硬化症 (MS) 的发病和进展.
- DNA甲基化 (DNAm) 模式因淋巴细胞亚型而异,与MS相关.
- 表观遗传衰老加速 (EAA) 估计生物年龄,并与各种健康状况有关.
研究的目的:
- 在患有多发性硬化症 (MS) 的个体中研究细胞特异性表观遗传衰老加速 (EAA).
- 确定EAA是否在MS病例和对照之间存在差异,并确定涉及的特定细胞类型.
主要方法:
- 一个用现有的DNA甲基化数据从Illumina 450K或EPIC阵列进行的病例对照研究.
- 使用GrimAge算法分析了来自583例多发性硬化病例和643例对照病例的全血DNA甲基化数据.
- 使用来自独立数据集的细胞分类DNA甲基化数据进行统计解卷和验证.
主要成果:
- 与对照组相比,患有多发性硬化症的个体显示EAA显著增加 (约. 9个月) 的时间.
- 具体来说,EAA与MS的相关性是依赖于B细胞的方式,独立于B细胞比例.
- 用B细胞丰富数据集的验证证实了MS病例的EAA大幅增加 (5.1年),而用T细胞丰富的数据集显示没有差异.
结论:
- 这项研究提供了强有力的证据,表明MS患者的B细胞中有明显的EAA.
- 结果支持这样一个假设:B细胞的过早免疫衰老有助于MS.
- 未来的MS研究应该调查B细胞内与年龄相关的分子机制.


