A quantitative analysis of oligodendrocytes in multiple sclerosis lesions -: A study of 113 cases
A quantitative analysis of oligodendrocytes in multiple sclerosis lesions -: A study of 113 cases
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DOI：
10.1093/brain/122.12.2279
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发表时间：
1999-12-01
期刊：
影响因子：
14.5
通讯作者：
Lassmann, H
中科院分区：
文献类型：
--
作者：
Lucchinetti, C;Brück, W;Lassmann, H
我们从113例多发性硬化患者的活检和尸检组织中定量研究了395个病变区的少突胶质细胞在病变形成过程中的去向。多发性硬化症病变中OGs的密度在脱髓鞘活动的所有阶段都是不同的，从几乎完全消失到超过斑块周围白质的值(范围0-970OGs/mm(2))。为了确定不同患者是否存在不同的OG病理类型，我们将分析限制在56例患者中，其中病变的纵向范围从斑块周围的白质延伸到活跃的脱髓鞘边缘和不活跃的斑块中心，OG病理的两个主要组被定义为病变内是否有OG增加，在70%(39/56)的病例中，OG在髓鞘破坏的活动期不同程度地减少，但在非活动或再髓鞘区域重新出现。在非活动区，与表达髓鞘少突胶质细胞糖蛋白(MOG)的OGs相比，表达蛋白脂蛋白(PLP)mRNA的OGs的数量增加，提示这些细胞可能来自祖细胞池。在其余30%(17/56)的病例中，观察到脱髓鞘活跃部位的髓鞘细胞广泛破坏，但在非活动斑块区域没有OGs而没有再髓鞘形成。在来自特定患者的所有皮损中，OG病理模式保持一致，皮损中巨噬细胞的数量与MOG和PLP mRNA标记的OGs数量呈高度显著的负相关(MOG：P=-0，32，P<；0.0000118；PLP mRNA：r=-0，23，P<；0,00238)，OG密度与T细胞和浆细胞炎症及轴突丢失无关。活动性脱髓鞘病变中OG破坏的程度和地形图的严重异质性表明，在多发性硬化症患者的亚群中，髓鞘、成熟OG和可能的OG前体细胞受到不同程度的影响。
We studied quantitatively the fate of oligodendrocytes (OGs) during lesion formation in 395 lesion areas from biopsy and autopsy tissue of 113 multiple sclerosis cases. The density of OGs in multiple sclerosis lesions was variable at all stages of demyelinating activity, ranging from nearly complete loss to values exceeding those in the periplaque white matter (range 0-970 OGs/mm(2)). To determine whether there were distinct patterns of OG pathology in different patients, we restricted our analysis to the 56 cases in which the longitudinal extent of the lesion extended from periplaque white matter into the active demyelinating edge and inactive plaque centre, Two major groups of OG pathology were defined by the presence or absence of increased OGs within the lesion, In 70% (39 out of 56) of the cases, OGs were variably reduced during active stages of myelin destruction, but reappeared within inactive or remyelinating areas. In inactive, areas, an increased number of OGs expressing proteolipid protein (PLP) mRNA compared with those expressing myelin oligodendrocyte glycoprotein (MOG) suggested these cells may have been derived from the progenitor pool In the remaining 30% (17 out of 56) of the cases, extensive destruction of myelinating cells at active sites of demyelination was observed, but OGs were absent in inactive plaque areas without remyelination, In all lesions from a given patient the pattern of OG pathology remained consistent, A highly significant negative correlation was observed between number of macrophages in lesions and number of MOG- and PLP mRNA-labelled OGs (MOG: p = -0,32, P < 0.0000118; PLP mRNA: r = -0,23, P < 0,00238), OG density did not correlate with T-cell and plasma cell inflammation, or axonal loss. The profound heterogeneity in extent and topography of OG destruction in active demyelinating lesions suggests that in subsets of multiple sclerosis patients, myelin, mature OGs and possibly OG progenitors are differentially affected.