Miescher G C, Steck A J
Department of Research, University Hospitals, Basel, Switzerland.
Baillieres Clin Neurol. 1996 Mar;5(1):219-32.
Paraproteinaemia and neuropathy are each relatively frequent and may be associated by chance. However, a number of significant relationships have to be ruled out in the differential diagnosis. Malignant gammopathy should be excluded: multiple myeloma can lead to compression of the spinal cord or cauda equina; primary amyloidosis is occasionally involved; the rare but intriguing POEMS syndrome, consisting of polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes, usually accompanies osteosclerotic myeloma. It can be associated with angio-follicular lymph node hyperplasia and needs to be recognized because radioablative therapy is curative. The 'benign' monoclonal gammopathies of undetermined significance, known as MGUS, are much more frequent. There is an IgM MGUS group with predominantly distal sensorimotor demyelinating polyneuropathy and another rather heterogeneous group with IgG or IgA MGUS and a tendency to a favourable response to plasmapheresis. The role of the monoclonal IgG and IgA antibodies is unclear. This chapter has focused on the pathogenetic mechanisms of neuropathies associated with IgM MGUS. In the majority of cases, monoclonal autoantibodies specific for particular carbohydrate epitopes bind to myelin and are now recognized as the primary cause of the disease manifestations, including widening of the myelin lamellae. While the autoantibodies have been shown to bind complement, the presence of inhibitors is invoked to explain the absence of acute inflammatory changes. The epitopes recognized with the highest affinity by the auto-antibodies are present on the myelin-associated glycoprotein (MAG) and could interfere with cell adhesion and cellular signally processes. In addition, binding to antigenically similar glycoproteins, such as PO, PMP-22 and some acidic glycolipids, may be a contributory factor. It is generally accepted that the anti-MAG autoantibodies are inducing a progressive demyelinating polyneuropathy by modifying axon-Schwann cell interactions.
副蛋白血症和神经病变都较为常见，可能偶然同时出现。然而，在鉴别诊断中必须排除一些重要的关联。应排除恶性丙种球蛋白病：多发性骨髓瘤可导致脊髓或马尾受压；原发性淀粉样变性偶尔也会累及；罕见但引人关注的POEMS综合征，包括多发性神经病变、器官肿大、内分泌病变、M蛋白和皮肤改变，通常与骨硬化性骨髓瘤相关。它可能与血管滤泡性淋巴结增生有关，需要被识别出来，因为放射消融治疗是有效的。意义未明的“良性”单克隆丙种球蛋白病，即MGUS，更为常见。有一个以远端感觉运动性脱髓鞘性多发性神经病变为主的IgM MGUS组，以及另一个由IgG或IgA MGUS组成的相当异质的组，对血浆置换有较好反应倾向。单克隆IgG和IgA抗体的作用尚不清楚。本章重点关注与IgM MGUS相关的神经病变的发病机制。在大多数情况下，针对特定碳水化合物表位的单克隆自身抗体与髓磷脂结合，现在被认为是疾病表现的主要原因，包括髓鞘板层增宽。虽然已证明自身抗体可结合补体，但需借助抑制剂的存在来解释为何没有急性炎症变化。自身抗体以最高亲和力识别的表位存在于髓鞘相关糖蛋白（MAG）上，可能会干扰细胞黏附和细胞信号传导过程。此外，与抗原性相似的糖蛋白，如PO、PMP - 22和一些酸性糖脂结合，可能也是一个促成因素。人们普遍认为，抗MAG自身抗体通过改变轴突 - 施万细胞相互作用引发进行性脱髓鞘性多发性神经病变。
