Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Scand J Immunol. 2023 Nov;98(5):e13325. doi: 10.1111/sji.13325. Epub 2023 Aug 21.
The clinical pattern in relapsing/remitting multiple sclerosis may be accounted for if an autoreactive immune response can transition back and forth between inflammatory, pathogenic, and non-inflammatory, non-pathogenic modes. Such 'back-and-forth' immune responses are rare. I speculate how such back-and-forth immune responses may arise. Understanding the nature of these different modes, and what controls their mutual transition, may help in designing strategies to favour the nonpathogenic mode, thus constituting treatment. Antigen dose is known to be critical in determining the class/subclass of primary immune responses. Observations have led us to suggest the level of antigen also similarly influences the class/subclass of on-going immune responses. I propose the relapsing, inflammatory and the remitting modes are respectively sustained by relatively low and high amounts of the responsible autoantigens, as is the case, for example, for Th1 and Th2 responses to foreign antigens. In addition, I propose more self-antigens are released during an inflammatory than during a remitting mode. The decrease in the amount of antigen released, as the response transitions from an inflammatory to a remitting mode, results in time in a decreased level of antigen and so the response again evolves towards the inflammatory mode. The inflammatory mode then leads to an increased release of antigen and so, in time, to remission. This model thus explains the transition between different modes. I outline non-invasive, testable predictions of the hypothesis. If confirmed, it may be ethical to examine whether the non-inflammatory mode can be sustained by administering myelin antigens during the remitting phase.
如果自身免疫反应能够在炎症性、致病性和非炎症性、非致病性模式之间来回转换，那么复发缓解型多发性硬化症的临床模式就可以得到解释。这种“来回”的免疫反应是很少见的。我推测这种来回的免疫反应是如何产生的。了解这些不同模式的性质，以及控制它们相互转换的因素，可能有助于设计有利于非致病性模式的策略，从而构成治疗方法。抗原剂量在决定原发性免疫反应的类别/亚类方面是至关重要的。观察结果使我们认为抗原水平同样也会影响正在进行的免疫反应的类别/亚类。我提出，复发、炎症和缓解模式分别由相对较低和较高量的自身抗原维持，这与 Th1 和 Th2 对外国抗原的反应是一样的。此外，我还提出在炎症模式期间比在缓解模式期间释放更多的自身抗原。随着反应从炎症模式向缓解模式转变，抗原释放量减少，导致抗原水平降低，因此反应再次向炎症模式演变。炎症模式随后导致抗原释放增加，从而随着时间的推移缓解。因此，该模型解释了不同模式之间的转换。我概述了该假设的非侵入性、可测试的预测。如果得到证实，那么在缓解期给予髓鞘抗原以维持非炎症模式可能在伦理上是可以接受的。
