Schäfer K H, Klotz M, Mergner D, Mestres P, Schimrigk K, Blaes F
Department of Child Surgery, Mannheim University Hospital, Mannheim, D-68167, Germany.
J Autoimmun. 2000 Dec;15(4):479-84. doi: 10.1006/jaut.2000.0454.
Autoantibodies against neuronal and tumour proteins have been described in many paraneoplastic neurological syndromes (PNS), but it is not clear whether these antibodies are pathogenic or simply a useful diagnostic tool. We took seven sera that were positive on routine screening for antineuronal antibodies and the IgG fractions. As controls we used sera from health blood-donors, other neurological autoimmune diseases and patients with SCLC without PNS. We tested them on dissociated rat myenteric plexus cultures for cytotoxic effects. After incubation for 24 h, cytotoxicity was determined by a double fluorescence test (calcein green for living cells and ethidium homodimer-1 for dead cells). We found an increased cell death rate in cultures incubated with the PNS sera, compared with all controls (P< 0.05). Isolated IgG fractions were also cytotoxic whereas the IgG-free serum fraction did not show any significant increase in cytotoxicity. After incubation with PNS IgG, FACS analysis revealed an increased cytotoxicity rate only of the neurones, but not the glial cells. Our results indicate that in PNS a complement-independent, antibody-mediated cytotoxicity against neurones may contribute to the pathogenesis of these syndromes.
在许多副肿瘤性神经系统综合征（PNS）中都已发现针对神经元和肿瘤蛋白的自身抗体，但尚不清楚这些抗体是致病性的还是仅仅是一种有用的诊断工具。我们选取了7份在抗神经元抗体常规筛查中呈阳性的血清及其IgG组分。作为对照，我们使用了健康献血者、其他神经自身免疫性疾病患者以及无PNS的小细胞肺癌（SCLC）患者的血清。我们在解离的大鼠肠肌丛培养物上测试了它们的细胞毒性作用。孵育24小时后，通过双荧光试验（活细胞用钙黄绿素，死细胞用碘化丙啶二聚体-1）测定细胞毒性。我们发现，与所有对照相比，用PNS血清孵育的培养物中细胞死亡率增加（P<0.05）。分离出的IgG组分也具有细胞毒性，而不含IgG的血清组分未显示出细胞毒性有任何显著增加。用PNS IgG孵育后，流式细胞术分析显示仅神经元的细胞毒性率增加，而神经胶质细胞未增加。我们的结果表明，在PNS中，一种不依赖补体的、抗体介导的针对神经元的细胞毒性可能促成了这些综合征的发病机制。
