RT期刊文章SR电子T1评价特异性表观遗传多发性硬化症患者年龄加速度摩根富林明神经病学神经学乔FD Lippincott Williams &威尔金斯10.1212 SP / WNL。首页0000000000207489 10.1212 / WNL。0000000000207489 A1维基Maltby A1亚历山大·泽维尔A1 Ewoud尤因A1 Maria-Pia平原A1 Sandeep Sampangi A1罗德尼·斯科特A1赫尔穆特•Butzkueven A1 Vilija Jokubaitis A1劳拉Kular A1 Steffan Bos A1马克睡A1英格丽·a·范德梅A1布鲁斯·V·泰勒(A1 wood Ponsonby A1 Maja Jagodic A1罗德尼Lea A1 Jeannette Lechner-Scott年2023 UL //www.ez-admanager.com/content/early/2023/08/04/WNL.0000000000207489.abstract AB背景:在多发性硬化症(MS)、首页免疫系统的加速老化(免疫衰老)可能与疾病发作或有关推动进展。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%置信区间ci: 3.6 - -14.4), P = 0.001)。统计性反褶积与显示,监管局女士B细胞依赖的方式(βint = 1.7, 95% ci: 0.3—-2.8), P = 0.002),无论B细胞比例。 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 = 5.5×10-5). 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 = 7.2×10-5), 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.

map