@article {Maltby10.1212 / WNL。0000000000207489,作者={维基Maltby亚历山大·泽维尔和Ewoud尤因Maria-Pia平原Sandeep Sampangi和罗德尼·斯科特和赫尔穆特•Butzkueven Vilija Jokubaitis和劳拉Kular Steffan Bos和马克和英格丽·a·范德梅和布鲁斯·V·泰勒和wood Ponsonby和Maja Jagodic罗德尼Lea和珍妮特Lechner-Scott}, title ={评价特异性表观遗传多发性硬化症患者年龄加速度},elocation-id = {10.1212 / WNL。={2023}0000000000207489},年,doi = {10.1212 / WNL。出版商0000000000207489}= {Wolters Kluwer健康,公司代表美国神经病学学会},文摘={背景:在多发性硬化症(MS)、免疫系统的加速老化(免疫衰老)可能与疾病发作或驱首页动发展。DNA甲基化(DNAm)是一种表观遗传因素不同淋巴细胞亚型中,和细胞中特定DNAm与DNAm女士不同的寿命和可用于准确地估计生理年龄加速度与一系列的障碍。目的:检测细胞特殊的表观遗传MS.Methods患者年龄加速度(EAA):这是一个病例对照,研究监管局使用现有DNAm几个独立的数据,先前发表的研究。数据包括如果.idat文件从Illumina公司450 k或史诗阵列可用一个女士的例子和一个年龄和性别匹配的控制,同样的研究。多因素统计模型进行评估监管的主要结果。我们探索监管局的关系和女士,包括交互识别特定免疫细胞的影响。细胞DNA甲基化数据分类三个独立数据集被用来验证结果。结果:我们使用全血DNA甲基化数据从583例和643非MS女士控制使用GrimAge算法计算监管局。MS组相比,表现出增加监管控制(\ ~ {}9 m, 95 \ % CI: 3.6 - -14.4), P = 0.001)。 Statistical deconvolution showed that EAA is associated with MS in a B cell dependent manner (βint=1.7, 95\%CI: 0.3-2.8), P = 0.002), irrespective of B cell proportions. Validation analysis using three independent datasets enriched for B cells, showed an EAA increase of 5.1yrs in MS compared to controls (95\%CI: 2.8-7.4, P = 5.5{\texttimes}10-5). By comparison, there was no EAA difference in MS in a T cell enriched dataset. We found that EAA was attributed to the DNAm surrogates for Beta-2-microglobulin (difference = 47,546, 95\%CI: 10,067-85,026; P = 7.2{\texttimes}10-5), and smoking pack years (difference = 8.1, 95\%CI: 1.9-14.2, P = 0.002).Conclusion: This study provides compelling evidence that B cells exhibit marked EAA in MS and supports the hypothesis that premature B cell immune senescence plays a role in MS. Future MS studies should focus on age-related molecular mechanisms in B cells.}, issn = {0028-3878}, URL = {//www.ez-admanager.com/content/early/2023/08/04/WNL.0000000000207489}, eprint = {//www.ez-admanager.com/content/early/2023/08/04/WNL.0000000000207489.full.pdf}, journal = {Neurology} }