Immunoglobulins and Complement in Postmortem Multiple Sclerosis Tissue
Immunoglobulins and Complement in Postmortem Multiple Sclerosis Tissue
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DOI：
10.1002/ana.21524
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发表时间：
2009-01-01
影响因子：
11.2
通讯作者：
Prineas, John W.
中科院分区：
文献类型：
--
作者：
Barnett, Michael H.;Parratt, John D. E.;Prineas, John W.
目的：通过分析多发性硬化症 (MS) 病例以及已知在大脑和脊髓中表达病毒和自身抗原的对照炎症性白质疾病的组织中免疫球蛋白和补体的分布，确定多发性硬化症 (MS) 中离散、特异性免疫反应的证据。方法：对 25 名多发性硬化症患者和 24 名患有其他神经系统疾病的患者的尸检组织进行免疫组织化学检查，以了解免疫球蛋白和活化补体（C3d 和 C9neo）。结果：在组织中远离多发性硬化症和其他神经系统疾病的局灶性病变，在许多正常结构中检测到 IgG，但在髓磷脂或分支小胶质细胞中未检测到。髓磷脂活跃分解区域和吞噬细胞中的髓磷脂被破坏，C3d 和 C9neo 呈阳性染色，多发性硬化症和所有其他检查的神经系统疾病（包括缺血性梗塞）中的 IgG 染色呈模棱两可。在进行性多灶性白质脑病、亚急性硬化性全脑炎和巨细胞病毒脑炎的病毒感染细胞中检测到疾病特异性 IgG 或补体沉积；视神经脊髓炎的神经胶质限制膜；以及阿尔茨海默氏痴呆症的老年斑。 MS 特有的异常小胶质细胞结节，在位于正常斑块周围白质的部分脱髓鞘轴突上含有短的、线性的激活补体 (C3d) 沉积物。 解释：MS 病变中受损髓磷脂的 IgG 和补体免疫染色，经常被引用为致病性抗髓磷脂抗体的指示，是一种非特异性特征，不能解释为独特发病机制的证据，也不能用于定义该疾病的特定变异。本研究中描述的异常小胶质细胞结节可能构成多发性硬化症中具有发病意义的特定生物标志物。
Objective: To identify evidence of a discrete, specific immune response in multiple sclerosis (MS) by analyzing the distribution Of immunoglobulins and complement in tissue derived from cases of MS, and from control inflammatory white matter diseases known to express viral and autoantigens in the brain and spinal cord.Methods: Autopsy tissue from 25 MS patients and 24 patients with other neurological diseases was examined immunohistochemically for immunoglobulins and activated complement (C3d and C9neo).Results: In tissue remote from focal lesions in MS and other neurological diseases, IgG was detected in many normal structures but not in myelin or ramified microglia. Disrupted myelin in areas of active myelin breakdown and in phagocytes stained positively for C3d and C9neo, and equivocally for IgG in MS and all other neurological diseases examined, including ischemic infarcts. Disease-specific deposits of IgG or complement were detected in virus-infected cells in progressive multifocal leukoencephalopathy, subacute sclerosing panencephalitis, and cytomegalovirus encephalitis; in glial-limiting membranes in neuromyelitis optica; and in senile plaques in Alzheimer's dementia. Specific to MS were unusual microglial nodules containing short, linear deposits of activated complement (C3d) on partly demyelinated axons located in normal-appearing periplaque white matter.Interpretation: IgG and complement immunostaining of disrupted myelin in MS lesions, frequently cited as an indication of pathogenic anti-myelin antibodies, is a nonspecific feature that cannot be interpreted as evidence of a distinct pathogenesis or serve to define particular variants of the disease. The unusual microglial nodules described in this study may constitute a specific biomarker with pathogenetic significance in MS.