THE INFLAMMATORY MYELINOPATHY OF ADRENOLEUKODYSTROPHY - CELLS, EFFECTOR MOLECULES, AND PATHOGENETIC IMPLICATIONS
THE INFLAMMATORY MYELINOPATHY OF ADRENOLEUKODYSTROPHY - CELLS, EFFECTOR MOLECULES, AND PATHOGENETIC IMPLICATIONS
复制标题
DOI：
10.1097/00005072-199211000-00007
复制
发表时间：
1992-11-01
影响因子：
3.2
通讯作者：
MOSER, HW
中科院分区：
文献类型：
--
作者：
POWERS, JM;LIU, Y;MOSER, HW
肾上腺脑白质营养不良（ALD）脱髓鞘病变中的显著炎症提示免疫介导的致病成分。将针对T细胞、B细胞、巨噬细胞、I类和II类分子、补体、IgG、IgM、伊加、白细胞介素-1（IL-1）、细胞间粘附分子-1（ICAM-1）和肿瘤坏死因子-α（TNF）的市售抗体应用于甲醛固定的尸检样本的石蜡切片。25个原发性脱髓鞘病变从五个青少年ALD，三个成人ALD，和三个肾上腺脊髓神经病患者进行了评价与适当的阳性和阴性对照。巨噬细胞和星形胶质细胞是在活动边缘检测到的主要细胞; T淋巴细胞，包括T4和CD 45 R亚群，几乎一样多，但通常位于病变内的血管周围。通常含有IgG的B细胞和浆细胞不常见。II类分子的表达，仅限于一个成年人，是有问题的; I类表达增加微血管和其他细胞。降解的髓鞘标记C3 d和IL-1的抗体，IL-1和ICAM-1的免疫反应被认为是微血管和星形胶质细胞。在巨噬细胞中检测到肿瘤坏死因子-α免疫反应性，但在星形胶质细胞中更明显。这些数据支持ALD脱髓鞘病变中的天然免疫应答，主要由反应性星形胶质细胞、巨噬细胞、T细胞和细胞因子组成。两个阶段的发病理论进行了讨论。TNF和反应性星形胶质细胞的假定作用，与一个基本的髓鞘溶解性生化缺陷，提出了不同的发病机制，并提出了新的治疗可能性。
Prominent inflammation in the demyelinative lesion of adreno-leukodystrophy (ALD) has suggested an immune-mediated pathogenetic component. Commercially available antibodies to T cells, B cells, macrophages, class I and II molecules, complement, IgG, IgM, IgA, interleukin-1 (IL-1), intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-alpha (TNF) were applied to paraffin sections of formaldehyde-fixed postmortem samples. Twenty-five primary demyelinative lesions from five juvenile ALD, three adult ALD, and three adrenomyeloneuropathic patients were evaluated with appropriate positive and negative controls. Macrophages and astrocytes were the predominant cells detected at the active edge; T lymphocytes, including T4 and CD45R subsets, were nearly as numerous but usually located around vessels within the lesion. B cells and plasma cells, usually containing IgG, were uncommon. The expression of class II molecules, restricted to one adult, was problematic; class I expression was increased in microvascular and other cells. Degraded myelin was labeled with antibodies to C3d and IL-1; IL-1 and ICAM-1 immunoreactivity was seen on microvessels and astrocytes. Tumor necrosis factor-alpha immunoreactivity was detected in macrophages, but more prominently in astrocytes. These data support a natural immune response in the demyelinative lesion of ALD, consisting predominantly of reactive astrocytes, macrophages, T cells and cytokines. A two-stage pathogenetic theory is discussed. The postulated roles of TNF and reactive astrocytes, in concert with a fundamental myelinolytic biochemical defect, suggest a different pathogenetic mechanism and raise novel therapeutic possibilities.