't Hart Bert A
University of Groningen, University Medical Center, Department of Neuroscience, Groningen, The Netherlands
Mult Scler. 2016 Apr;22(4):559-63. doi: 10.1177/1352458515591862. Epub 2015 Jun 25.
Multiple sclerosis (MS) develops exclusively in humans. Non-human primates are resistant against MS, although they are highly susceptible to the MS animal model, experimental autoimmune encephalomyelitis (EAE). Unravelling of the cause(s) underlying this discrepancy is highly relevant as insights might be gained into the elusive event(s) that trigger(s) MS. A well-established difference between the human primate (Homo sapiens) and non-human primates is that humans are unable to synthesize the sialic acid N-glycolylneuraminic acid (Neu5Gc).
We propose the concept that long-term ingestion by human primates of the foreign Neu5Gc, via red meat consumption, is an ignored environmental risk factor for MS. Conceptually, incorporation of dietary Neu5Gc into vital regions of the central nervous system, such as the blood-brain barrier (BBB) and the axon-myelin unit, creates targets for binding of de novo synthesized heterophilic anti-NeuGc antibodies. Binding of the antibodies can cause BBB leakage and destabilization of the axon-myelin coupling. The ensuing cytodegeneration and release of self-antigens could be a start of the characteristic pathological features of MS.
多发性硬化症（MS）仅在人类中发病。非人灵长类动物对MS具有抗性，尽管它们对MS动物模型实验性自身免疫性脑脊髓炎（EAE）高度易感。揭示这种差异背后的原因具有高度相关性，因为这可能有助于深入了解引发MS的难以捉摸的事件。人类灵长类动物（智人）与非人灵长类动物之间一个已确定的差异是，人类无法合成唾液酸N-羟乙酰神经氨酸（Neu5Gc）。
我们提出这样一个概念，即人类灵长类动物通过食用红肉长期摄入外来的Neu5Gc是MS一个被忽视的环境风险因素。从概念上讲，饮食中的Neu5Gc掺入中枢神经系统的重要区域，如血脑屏障（BBB）和轴突-髓鞘单元，会产生新合成的异嗜性抗NeuGc抗体的结合靶点。抗体的结合可导致BBB渗漏和轴突-髓鞘耦合不稳定。随之而来的细胞变性和自身抗原的释放可能是MS特征性病理特征的开端。
