Nobile-Orazio E, Manfredini E, Carpo M, Meucci N, Monaco S, Ferrari S, Bonetti B, Cavaletti G, Gemignani F, Durelli L
Institute of Clinical Neurology, Centro Dino Ferrari, Ospedale Maggiore-Policlinico, University of Milan, Italy.
Ann Neurol. 1994 Sep;36(3):416-24. doi: 10.1002/ana.410360313.
We studied the frequency and clinical correlates of different IgM specificities in 75 patients with neuropathy associated with IgM monoclonal gammopathy. Patients were tested for IgM reactivity with the myelin-associated glycoprotein, P0, neurofilaments, and tubulin by immunoblot; with GM1, asialo-GM1, GM2, GD1a, GD1b, sulfatide, and chondroitin sulfate C by enzyme-linked immunosorbent assay; and with brain and nerve glycolipids by overlay high-performance thin-layer chromatography. Forty-two patients (56%) had high titers of IgM antibodies to MAG; 4 (5%), to sulfatide (1 also to myelin-associated glycoprotein); 4 (5%), to the 200-kd neurofilament (2 also to myelin-associated protein); and 1 each, to GD1b and chondroitin sulfate C. No reactivity was found in 26 patients (35%). More patients with anti-myelin-associated glycoprotein IgM (62%) than with unknown IgM reactivity (31%) had a predominantly sensory neuropathy (p < 0.025). Nerve conduction findings were consistent with a demyelinating neuropathy in 77% of patients reactive to myelin-associated glycoprotein and 24% with unknown reactivity (p < 0.0001) and the mean conduction velocity of peroneal nerve was lower in the former group (22.9 m/sec) than in the latter group (39.6 m/sec) (p < 0.000001). Patients with anti-sulfatide IgM had a sensorimotor neuropathy with morphological evidence of demyelination while anti-neurofilament IgM was not associated with homogeneous findings. Patients with anti-GD1b or anti-chondroitin sulfate C IgM had a predominantly motor impairment. The frequent occurrence of anti-neural IgM antibodies in neuropathy associated with IgM gammopathy, and their frequent, though not constant association with similar neuropathy features, support their possible pathogenetic role in the neuropathy.
我们研究了75例与IgM单克隆丙种球蛋白病相关的神经病变患者中不同IgM特异性的频率及其临床相关性。通过免疫印迹法检测患者的IgM与髓鞘相关糖蛋白、P0、神经丝和微管蛋白的反应性；通过酶联免疫吸附测定法检测其与GM1、脱唾液酸GM1、GM2、GD1a、GD1b、硫脂和硫酸软骨素C的反应性；通过覆盖高效薄层色谱法检测其与脑和神经糖脂的反应性。42例患者（56%）对MAG有高滴度IgM抗体；4例（5%）对硫脂有反应（1例同时对髓鞘相关糖蛋白有反应）；4例（5%）对200-kd神经丝有反应（2例同时对髓鞘相关蛋白有反应）；各有1例对GD1b和硫酸软骨素C有反应。26例患者（35%）未发现反应性。与IgM反应性未知的患者（31%）相比，更多抗髓鞘相关糖蛋白IgM的患者（62%）主要表现为感觉性神经病变（p<0.025）。在对髓鞘相关糖蛋白有反应的患者中，77%的神经传导结果符合脱髓鞘性神经病变，而反应性未知的患者中这一比例为24%（p<0.0001），且前一组腓总神经的平均传导速度（22.9米/秒）低于后一组（39.6米/秒）（p<0.000001）。抗硫脂IgM的患者有感觉运动性神经病变，并有脱髓鞘的形态学证据，而抗神经丝IgM则与一致的表现无关。抗GD1b或抗硫酸软骨素C IgM的患者主要有运动障碍。在与IgM丙种球蛋白病相关的神经病变中抗神经IgM抗体频繁出现，且它们频繁（尽管并非始终）与相似的神经病变特征相关，这支持它们在神经病变中可能的致病作用。
