Cavanna B, Jiang H, Allaria S, Carpo M, Scarlato G, Nobile-Orazio E
Giorgio Spagnol Service of Clinical Neuroimmunology, Milan, Italy.
J Neuroimmunol. 2001 Mar 1;114(1-2):226-31. doi: 10.1016/s0165-5728(00)00461-6.
Anti-GM2 IgM antibodies have been reported in some patients with dysimmune neuropathy or lower motor neuron syndrome. To determine whether these antibodies can induce complement-dependent cytolysis we performed a cytotoxicity assay on neuroblastoma cells with sera from seven patients with demyelinating dysimmune neuropathies and high titers of anti-GM2 IgM. As controls we used sera from seven patients with other anti-neural reactivities, six with the same neuropathies but no anti-GM2 or other anti-neural reactivity and from eight normal subjects. Of the seven positive sera tested, six induced complement-mediated cytotoxicity, while none of the controls had any relevant effect on neuroblastoma cells. Preincubation of positive sera with purified GM2 removed cytotoxic activity. Affinity purified anti-GM2 IgM had the same cytotoxic anti-GM2 effect of whole serum while serum or complement alone did not have any effect. In four anti-GM2-positive patients the percentage of cell lysis correlated with anti-GM2 titers and with IgM staining of neuroblastoma cells while in two the cytotoxic effect was higher than expected from antibody titers. Complement-mediated cell lysis induced by anti-GM2 IgM antibodies may be a possible mechanism of neural damage in patients with dysimmune neuropathy and high titers of anti-GM2 IgM antibodies.
在一些免疫失调性神经病或下运动神经元综合征患者中已报道存在抗GM2 IgM抗体。为了确定这些抗体是否能诱导补体依赖性细胞溶解，我们用来自7例脱髓鞘性免疫失调性神经病且抗GM2 IgM滴度高的患者的血清，对神经母细胞瘤细胞进行了细胞毒性试验。作为对照，我们使用了来自7例有其他抗神经反应性的患者、6例患有相同神经病但无抗GM2或其他抗神经反应性的患者以及8名正常受试者的血清。在所检测的7份阳性血清中，有6份诱导了补体介导的细胞毒性，而所有对照对神经母细胞瘤细胞均无相关影响。阳性血清与纯化的GM2预孵育可消除细胞毒性活性。亲和纯化的抗GM2 IgM具有与全血清相同的细胞毒性抗GM2作用，而单独的血清或补体则无任何作用。在4例抗GM2阳性患者中，细胞裂解百分比与抗GM2滴度以及神经母细胞瘤细胞的IgM染色相关，而在另外2例中，细胞毒性作用高于抗体滴度预期。抗GM2 IgM抗体诱导的补体介导的细胞裂解可能是免疫失调性神经病且抗GM2 IgM抗体滴度高的患者神经损伤的一种可能机制。
