Pathologic heterogeneity persists in early active multiple sclerosis lesions.
Pathologic heterogeneity persists in early active multiple sclerosis lesions.
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DOI：
10.1002/ana.24163
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发表时间：
2014-05
影响因子：
11.2
通讯作者：
Lucchinetti, Claudia F.
中科院分区：
文献类型：
--
作者：
Metz, Imke;Weigand, Stephen D.;Popescu, Bogdan F. G.;Frischer, Josa M.;Parisi, Joseph E.;Guo, Yong;Lassmann, Hans;Brueck, Wolfgang;Lucchinetti, Claudia F.
多发性硬化症(MS)的病变表现为脱髓鞘的免疫病理异质性。以往的横断面研究报道，同一个体的多个活动性脱髓鞘病变的脱髓鞘免疫表型相同，但个体间不同，从而导致了个体内病理同质性和个体间异质性的假说。其他研究小组则认为病变的异质性与时间有关。我们这项研究的目的是分析纵向收集的组织样本，以确定在特定患者中脱髓鞘的模式是否会随着时间的推移而持续。对经病理证实的中枢神经系统炎性脱髓鞘病患者的档案组织标本进行免疫组织化学分析。纳入标准是早期活动性脱髓鞘病变的存在--免疫模式分类所必需的--从同一患者在两个或更多时间点获得。在1321例符合多发性硬化症的手术活检中，22例符合研究纳入标准。21名患者(95%)在从不同时间点采集的组织中显示出持续的免疫病理模式。这种坚持性在所有主要的脱髓鞘类型中都得到了证明。1例患者在活检中表现出II型和III型的特征，但在尸检检查的所有活动性病变中只有II型。这些发现继续支持早期多发性硬化症患者依赖的免疫病理异质性的概念，并提示组织损伤的机制和靶点在患者亚组中可能不同。这些观察结果对个体化治疗方法具有潜在的重要意义。
Multiple sclerosis (MS) lesions demonstrate immunopathological heterogeneity in patterns of demyelination. Previous cross-sectional studies reported immunopatterns of demyelination were identical among multiple active demyelinating lesions from the same individual, but differed between individuals, leading to the hypothesis of intraindividual pathological homogeneity and interindividual heterogeneity. Other groups suggested a time-dependent heterogeneity of lesions. The objective of our present study was to analyze tissue samples collected longitudinally to determine whether patterns of demyelination persist over time within a given patient. Archival tissue samples derived from patients with pathologically confirmed CNS inflammatory demyelinating disease who had undergone either diagnostic serial biopsy or biopsy followed by autopsy, were analyzed immunohistochemically. Inclusion criteria was the presence of early active demyelinating lesions - required for immunopattern classification - obtained from the same patient at two or more time points. Among 1321 surgical biopsies consistent with MS, 22 cases met study inclusion criteria. Twenty-one patients (95%) showed a persistence of immunopathological patterns in tissue sampled from different time points. This persistence was demonstrated for all major patterns of demyelination. A single patient showed features suggestive of both pattern II and pattern III on biopsy, but only pattern II among all active lesions examined at autopsy. These findings continue to support the concept of patient-dependent immunopathological heterogeneity in early MS and suggest that the mechanisms and targets of tissue injury may differ among patient subgroups. These observations have potentially significant implications for individualized therapeutic approaches.
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影响因子：
11.2
作者：
POSER, CM;PATY, DW;TOURTELLOTTE, WW
通讯作者：
TOURTELLOTTE, WW
影响因子：
11.2
作者：
McDonald, WI;Compston, A;Wolinsky, JS
通讯作者：
Wolinsky, JS
影响因子：
9.9
作者：
Kitley, Joanna;Woodhall, Mark;Vincent, Angela
通讯作者：
Vincent, Angela
DOI：
10.1093/jnen/63.3.262
发表时间：
2004-03-01
影响因子：
3.2
作者：
Mahad, DJ;Trebst, C;Ransohoff, RM
通讯作者：
Ransohoff, RM
影响因子：
11.2
作者：
Breij, Esther C. W.;Brink, Bianca P.;Boe, Lars
通讯作者：
Boe, Lars