Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
Exp Neurol. 2012 Jan;233(1):534-42. doi: 10.1016/j.expneurol.2011.11.039. Epub 2011 Dec 8.
Autoantibodies against gangliosides GM1 or GD1a are associated with acute motor axonal neuropathy (AMAN) and acute motor-sensory axonal neuropathy (AMSAN), whereas antibodies to GD1b ganglioside are detected in acute sensory ataxic neuropathy (ASAN). These neuropathies have been proposed to be closely related and comprise a continuous spectrum, although the underlying mechanisms, especially for sensory nerve involvement, are still unclear. Antibodies to GM1 and GD1a have been proposed to disrupt the nodes of Ranvier in motor nerves via complement pathway. We hypothesized that the disruption of nodes of Ranvier is a common mechanism whereby various anti-ganglioside antibodies found in these neuropathies lead to nervous system dysfunction. Here, we show that the IgG monoclonal anti-GD1a/GT1b antibody injected into rat sciatic nerves caused deposition of IgG and complement products on the nodal axolemma and disrupted clusters of nodal and paranodal molecules predominantly in motor nerves, and induced early reversible motor nerve conduction block. Injection of IgG monoclonal anti-GD1b antibody induced nodal disruption predominantly in sensory nerves. In an ASAN rabbit model associated with IgG anti-GD1b antibodies, complement-mediated nodal disruption was observed predominantly in sensory nerves. In an AMAN rabbit model associated with IgG anti-GM1 antibodies, complement attack of nodes was found primarily in motor nerves, but occasionally in sensory nerves as well. Periaxonal macrophages and axonal degeneration were observed in dorsal roots from ASAN rabbits and AMAN rabbits. Thus, nodal disruption may be a common mechanism in immune-mediated neuropathies associated with autoantibodies to gangliosides GM1, GD1a, or GD1b, providing an explanation for the continuous spectrum of AMAN, AMSAN, and ASAN.
抗神经节苷脂 GM1 或 GD1a 的自身抗体与急性运动轴索性神经病（AMAN）和急性运动感觉轴索性神经病（AMSAN）有关，而抗 GD1b 神经节苷脂的抗体则存在于急性感觉运动性神经病（ASAN）中。这些神经病被认为密切相关，构成了一个连续的谱，尽管其潜在机制，特别是感觉神经受累的机制，仍不清楚。据报道，GM1 和 GD1a 抗体通过补体途径破坏运动神经中的Ranvier 结。我们假设，Ranvier 结的破坏是一种共同的机制，通过这种机制，这些神经病中发现的各种抗神经节苷脂抗体导致神经系统功能障碍。在这里，我们表明，注入大鼠坐骨神经的 IgG 单克隆抗-GD1a/GT1b 抗体导致 IgG 和补体产物在节结轴膜上沉积，并主要在运动神经中破坏节结和旁节结分子簇，导致早期可逆的运动神经传导阻滞。注射 IgG 单克隆抗-GD1b 抗体主要在感觉神经中引起节结破坏。在与 IgG 抗-GD1b 抗体相关的 ASAN 兔模型中，观察到补体介导的节结破坏主要发生在感觉神经中。在与 IgG 抗-GM1 抗体相关的 AMAN 兔模型中，发现补体攻击节结主要发生在运动神经中，但偶尔也发生在感觉神经中。在 ASAN 兔和 AMAN 兔的背根中观察到轴周巨噬细胞和轴突变性。因此，节结破坏可能是与 GM1、GD1a 或 GD1b 神经节苷脂自身抗体相关的免疫介导性神经病的共同机制，为 AMAN、AMSAN 和 ASAN 的连续谱提供了解释。
