Institute of Neurology, Medical University of Vienna, Vienna, Austria.
Glia. 2010 Nov 15;58(15):1847-57. doi: 10.1002/glia.21054.
Multiple sclerosis (MS) is an idiopathic chronic inflammatory demyelinating disease of the central nervous system with variable extent of remyelination. Remyelination originates from oligodendrocyte (OG) precursor cells, which migrate and differentiate into mature OG. Tubulin polymerization promoting protein (TPPP/p25) is located in mature OG and aggregates in oligodendroglial cytoplasmic inclusions in multiple system atrophy. We developed a novel monoclonal anti-TPPP/p25 antibody to quantify OG in different subtypes and disease stages of MS, and possible degenerative changes in OG. We evaluated autopsy material from 25 MS cases, including acute, primary progressive, secondary progressive, relapsing remitting MS, and five controls. Demyelinated lesions revealed loss of TPPP/p25-positive OG within the plaques. In remyelination, TPPP/p25 was first expressed in OG cytoplasms and later became positive in myelin sheaths. We observed increased numbers of TPPP/p25 immunoreactive OG in the normal appearing white matter (NAWM) in MS patients. In MS cases, the cytoplasmic area of TPPP/p25 immunoreactivity in the OG was higher in the periplaque area when compared with NAWM and the plaque, and TPPP/p25 immunoreactive OG cytoplasmic area inversely correlated with the disease duration. There was a lack of phospho-TDP-43, phospho-tau, α-synuclein, and ubiquitin immunoreactivity in OG with enlarged cytoplasm. Our data suggest impaired differentiation, migration, and activation capacity of OG in later disease stages of MS. Upregulation of TPPP/p25 in the periplaque white matter OG without evidence for inclusion body formation might reflect an activation state. Distinct and increased expression of TPPP/p25 in MS renders it a potential prognostic and diagnostic marker of MS.
多发性硬化症（MS）是一种特发性慢性中枢神经系统炎症性脱髓鞘疾病，具有不同程度的髓鞘再生。髓鞘再生源自少突胶质细胞（OG）前体细胞，其迁移并分化为成熟 OG。微管蛋白聚合促进蛋白（TPPP/p25）位于成熟 OG 中，并在多系统萎缩的少突胶质细胞质包涵体中聚集。我们开发了一种新型单克隆抗 TPPP/p25 抗体，用于定量 MS 的不同亚型和疾病阶段以及 OG 可能的退行性变化中的 OG。我们评估了 25 例 MS 病例的尸检材料，包括急性、原发性进行性、继发性进行性、复发缓解型 MS 和 5 例对照。脱髓鞘病变显示斑块内 TPPP/p25 阳性 OG 的缺失。在髓鞘再生过程中，TPPP/p25 首先在 OG 细胞质中表达，随后在髓鞘中呈阳性。我们观察到 MS 患者正常外观白质（NAWM）中 TPPP/p25 免疫反应性 OG 的数量增加。在 MS 病例中，与 NAWM 和斑块相比，OG 中 TPPP/p25 免疫反应性的细胞质区域在斑块周围区域更高，TPPP/p25 免疫反应性 OG 细胞质区域与疾病持续时间呈负相关。在细胞质增大的 OG 中未发现磷酸化 TDP-43、磷酸化 tau、α-突触核蛋白和泛素免疫反应性。我们的数据表明，在 MS 的晚期疾病阶段，OG 的分化、迁移和激活能力受损。斑块周围白质中 TPPP/p25 的上调而没有包涵体形成的证据可能反映了一种激活状态。MS 中 TPPP/p25 的独特上调使其成为 MS 的潜在预后和诊断标志物。
