Homogeneity of active demyelinating lesions in established multiple sclerosis
Homogeneity of active demyelinating lesions in established multiple sclerosis
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DOI：
10.1002/ana.21311
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发表时间：
2008-01-01
影响因子：
11.2
通讯作者：
Boe, Lars
中科院分区：
文献类型：
--
作者：
Breij, Esther C. W.;Brink, Bianca P.;Boe, Lars
目的：在多发性硬化症（MS）患者发病后不久进行活检的活动性脱髓鞘病变中描述了四种不同的脱髓鞘模式。这些模式被认为代表了潜在发病机制的异质性。本研究的目的是确定是否病变异质性也存在于尸检材料从患者建立MS.方法：所有MS脑组织可在VU医疗中心进行了评估活动性脱髓鞘病变的存在下，使用磁共振成像引导下的采样和免疫组化。使用组织学、免疫组织化学和共聚焦显微镜对含有活动性脱髓鞘病变的组织块进行评价，以确定是否存在补体和抗体沉积、少突胶质细胞凋亡、髓鞘蛋白差异丢失和缺氧样损伤。块与活动性脱髓鞘病变进行了比较块与活动性（nondemyelinating）和非活动性lesions.Results：补体和抗体始终与巨噬细胞在活动性脱髓鞘领域。髓鞘蛋白的优先丢失，广泛的缺氧样损伤和少突胶质细胞凋亡不存在或罕见。这种模式被观察到在所有组织块含有活动性脱髓鞘病变，病变异质性之间的patients.Interpretation：在建立MS的活动性脱髓鞘病变的免疫病理学表现是统一的。在MS病变形成的最早期，脱髓鞘病变的初始异质性可能会随着时间的推移而消失，因为不同的途径会聚集在一个脱髓鞘的一般机制中。吞噬巨噬细胞中补体、抗体和Fc γ受体的一致存在表明抗体和补体介导的髓鞘吞噬作用是已确立的MS脱髓鞘的主要机制。
Objective: Four different patterns of demyelination have been described in active demyelinating lesions of multiple sclerosis (MS) patients that were biopsied shortly after disease onset. These patterns were suggested to represent heterogeneity of the underlying pathogenesis. The aim of this study was to determine whether lesion heterogeneity also exists in an unselected collection of autopsy material from patients with established MS.Methods: All MS brain tissue available in the VU Medical Center was assessed for the presence of active demyelinating lesions using magnetic resonance imaging-guided sampling and immunohistochemistry. Tissue blocks containing active demyelinating lesions were evaluated for the presence of complement and antibody deposition, oligodendrocyte apoptosis, differential loss of myelin proteins, and hypoxia-like damage using histology, immunohistochemistry, and confocal microscopy. Blocks with active demyelinating lesions were compared with blocks with active (nondemyelinating) and inactive lesions.Results: Complement and antibodies were consistently associated with macrophages in areas of active demyelination. Preferential loss of myelin proteins, extensive hypoxia-like damage, and oligodendrocyte apoptosis were absent or rare. This pattern was observed in all tissue blocks containing active demyelinating lesions; lesion heterogeneity between patients was not found.Interpretation: The immunopathological appearance of active demyelinating lesions in established MS is uniform. Initial heterogeneity of demyelinating lesions in the earliest phase of MS lesion formation may disappear over time as different pathways converge in one general mechanism of demyelination. Consistent presence of complement, antibodies, and Fc gamma receptors in phagocytic macrophages suggests that antibody- and complement-mediated myelin phagocytosis is the dominant mechanism of demyelination in established MS.