Lopez Pablo H H, Comín Romina, Villa Andres M, Di Egidio Mariana, Saizar Roberto D, Sica Roberto E P, Nores Gustavo A
Departamento de Química Biológica Dr. Ranwel Caputto, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba and CIQUIBIC, CONICET, Ciudad Universitaria, Cordóba-5000, Argentina.
Biochim Biophys Acta. 2006 Mar;1762(3):357-61. doi: 10.1016/j.bbadis.2005.11.005. Epub 2005 Dec 13.
High titers of anti-GA1 antibodies have been associated with neurological syndromes. In most cases, these antibodies cross-react with the structurally related glycolipids GM1 and GD1b, although specific anti-GA1 antibodies have also been reported. The role of specific anti-GA1 antibodies is uncertain since the presence of GA1 in the human nervous system has not been clarified. A rabbit was immunized with GD1a and its sera were screened for antibody reactivity by standard immunoassay methods (HPTLC-immunostaining and ELISA). Anti-GD1a antibodies were not detected but, unexpectedly, anti-GA1 IgG-antibodies were found. Antibody binding to GA1 was inhibited by soluble GA1 but also by GD1a. These results indicate that the rabbit produced antibodies that recognize epitopes present on the glycolipids, that are absent or not exposed on solid phase adsorbed GD1a. We investigated the presence of these unusual anti-ganglioside antibodies in normal and neurological patient sera. Approximately, 10% of normal human sera contained low titer of specific anti-GA1 IgG-antibodies but none of them recognized soluble GD1a. High titers of IgG-antibodies reacting only with GA1 were detected in 12 patient sera out of 325 analyzed. Of these, 6 sera showed binding that was inhibited by soluble GD1a and four of them also by GM1. This new type of anti-ganglioside antibodies should be considered important elements for understanding of the pathogenesis of these diseases as well as their diagnosis.
高滴度的抗GA1抗体与神经综合征有关。在大多数情况下，这些抗体与结构相关的糖脂GM1和GD1b发生交叉反应，不过也有特异性抗GA1抗体的报道。由于人类神经系统中GA1的存在尚未明确，特异性抗GA1抗体的作用尚不确定。用GD1a免疫一只兔子，并通过标准免疫测定方法（高效薄层层析免疫染色和酶联免疫吸附测定）筛选其血清中的抗体反应性。未检测到抗GD1a抗体，但意外地发现了抗GA1 IgG抗体。与GA1的抗体结合被可溶性GA1抑制，但也被GD1a抑制。这些结果表明，兔子产生的抗体识别糖脂上存在的表位，而这些表位在固相吸附的GD1a上不存在或未暴露。我们研究了正常人和神经疾病患者血清中这些异常抗神经节苷脂抗体的存在情况。大约10%的正常人血清含有低滴度的特异性抗GA1 IgG抗体，但它们均不识别可溶性GD1a。在325份分析的患者血清中，有12份检测到仅与GA1反应的高滴度IgG抗体。其中，6份血清显示结合被可溶性GD1a抑制，其中4份也被GM1抑制。这种新型抗神经节苷脂抗体应被视为理解这些疾病发病机制及其诊断的重要因素。
