Vlata Zaharenia, Tsatsakis Aristidis, Tzagournissakis Minas, Krambovitis Elias
Department of Applied Biochemistry and Immunology, Institute of Molecular Biology and Biotechnology, Vassilika Vouton, Heraklion, Crete, Greece.
Endocr Metab Immune Disord Drug Targets. 2012 Sep;12(3):268-73. doi: 10.2174/187153012802002893.
Botulinum neurotoxins (BoNTs) are used in the treatment of many neurological disorders. The primary structure of BoNTs shows a high degree of homology with the tetanus neurotoxin, the toxoid of which is used as a vaccine. Because of the potential cross-reactivity between these toxins, we investigated the effects of Botulinum neurotoxin A (BoNT/A) and tetanus toxoid on peripheral blood mononuclear cells (PBMC) and the corresponding serum antibody levels, in twenty patients who had been treated with BoNT/A. We observed very low PBMC immunostimulation by BoNT/A at the tested dose (15 units/ml), as demonstrated by the low lymphocyte proliferation, and the absence of detectable antibodies cross-reacting with tetanus. However, exposure of PBMC from tetanus-sensitized patients to both neurotoxins showed that BoNT/A exerted a co stimulatory effect on tetanus-stimulated cells. Interestingly, in flow cytometry analysis, BoNT/A seemed to also alter the ratio of naïve (CD45RA) : memory/effector (CD45RO) T lymphocyte subsets, in favour of CD45RO. These preliminary data give a new insight on the potential immune crossreactivity between the two antigens. In view of the wide use of both neurotoxins, these immunotoxic effects merit a more detailed investigation.
肉毒杆菌神经毒素（BoNTs）被用于治疗多种神经系统疾病。BoNTs的一级结构与破伤风神经毒素高度同源，破伤风神经毒素的类毒素被用作疫苗。由于这些毒素之间可能存在交叉反应，我们研究了肉毒杆菌神经毒素A（BoNT/A）和破伤风类毒素对20例接受过BoNT/A治疗患者的外周血单核细胞（PBMC）及相应血清抗体水平的影响。我们观察到，在测试剂量（15单位/毫升）下，BoNT/A对PBMC的免疫刺激作用非常低，淋巴细胞增殖率低以及未检测到与破伤风交叉反应的抗体就证明了这一点。然而，将破伤风致敏患者的PBMC暴露于两种神经毒素中发现，BoNT/A对破伤风刺激的细胞具有共刺激作用。有趣的是，在流式细胞术分析中，BoNT/A似乎还改变了初始（CD45RA）：记忆/效应（CD45RO）T淋巴细胞亚群的比例，有利于CD45RO。这些初步数据为这两种抗原之间潜在的免疫交叉反应提供了新的见解。鉴于这两种神经毒素的广泛使用，这些免疫毒性作用值得更详细的研究。
