Accumulation of meningeal lymphocytes correlates with white matter lesion activity in progressive multiple sclerosis.
Accumulation of meningeal lymphocytes correlates with white matter lesion activity in progressive multiple sclerosis.
复制标题
DOI：
10.1172/jci.insight.151683
复制
发表时间：
2022-03-08
期刊：
影响因子：
8
通讯作者：
Ramaglia V
中科院分区：
文献类型：
--
作者：
Ahmed SM;Fransen NL;Touil H;Michailidou I;Huitinga I;Gommerman JL;Bar-Or A;Ramaglia V
枕下皮质脱髓鞘是多发性硬化症（MS）病理中导致疾病进展的重要组成部分，但其发展的机制尚不清楚。涉及脑膜的区隔性炎症可导致这种类型的损伤。鉴于最近发现进展性MS患者中存在大量白质（WM）病变活动，阐明WM病变活动是否以及如何与脑膜炎症和枕下皮质损伤相关是我们感兴趣的。我们对27例进展性MS患者分别使用死后FFPE组织块（范围5-72块，中位数30块），评估脑膜炎症、枕下皮质脱髓鞘程度和皮质下WM病变活动状态之间的关系。脑膜上T细胞和B细胞的聚集，而不是髓细胞的聚集，在空间上与枕下皮质病变相邻，免疫细胞的聚集越大，枕下病变面积越大。脑膜炎症程度较高的患者，活动性和混合性活动性/非活动性WM病变的比例更高，而非活动性和再髓化WM病变的总体比例较低。我们的研究结果支持脑膜淋巴细胞参与枕下皮质损伤，并指出炎症性枕下皮质脱髓鞘与皮层下WM发生的病理机制之间的潜在联系。
Subpial cortical demyelination is an important component of multiple sclerosis (MS) pathology contributing to disease progression, yet mechanism(s) underlying its development remain unclear. Compartmentalized inflammation involving the meninges may drive this type of injury. Given recent findings identifying substantial white matter (WM) lesion activity in patients with progressive MS, elucidating whether and how WM lesional activity relates to meningeal inflammation and subpial cortical injury is of interest. Using postmortem FFPE tissue blocks (range, 5–72 blocks; median, 30 blocks) for each of 27 patients with progressive MS, we assessed the relationship between meningeal inflammation, the extent of subpial cortical demyelination, and the state of subcortical WM lesional activity. Meningeal accumulations of T cells and B cells, but not myeloid cells, were spatially adjacent to subpial cortical lesions, and greater immune cell accumulation was associated with larger subpial lesion areas. Patients with a higher extent of meningeal inflammation harbored a greater proportion of active and mixed active/inactive WM lesions and an overall lower proportion of inactive and remyelinated WM lesions. Our findings support the involvement of meningeal lymphocytes in subpial cortical injury and point to a potential link between inflammatory subpial cortical demyelination and pathological mechanisms occurring in the subcortical WM.