Bolton Christopher
Solupharm Limited UK, Monarch House, Bristol, BS3 2BX, UK.
Immun Ageing. 2021 Apr 14;18(1):18. doi: 10.1186/s12979-021-00225-0.
The pathogenesis of the human demyelinating disorder multiple sclerosis (MS) involves the loss of immune tolerance to self-neuroantigens. A deterioration in immune tolerance is linked to inherent immune ageing, or immunosenescence (ISC). Previous work by the author has confirmed the presence of ISC during MS. Moreover, evidence verified a prematurely aged immune system that may change the frequency and profile of MS through an altered decline in immune tolerance. Immune ageing is closely linked to a chronic systemic sub-optimal inflammation, termed inflammageing (IFA), which disrupts the efficiency of immune tolerance by varying the dynamics of ISC that includes accelerated changes to the immune system over time. Therefore, a shifting deterioration in immunological tolerance may evolve during MS through adversely-scheduled effects of IFA on ISC. However, there is, to date, no collective proof of ongoing IFA during MS. The Review addresses the constraint and provides a systematic critique of compelling evidence, through appraisal of IFA-related biomarker studies, to support the occurrence of a sub-optimal inflammation during MS. The findings justify further work to unequivocally demonstrate IFA in MS and provide additional insight into the complex pathology and developing epidemiology of the disease.
人类脱髓鞘疾病多发性硬化症(MS)的发病机制涉及对自身神经抗原免疫耐受性的丧失。免疫耐受性的恶化与内在免疫衰老或免疫衰老(ISC)有关。作者之前的研究证实了MS期间存在ISC。此外,有证据证实免疫系统过早衰老,这可能通过改变免疫耐受性的下降频率和特征来改变MS的病程。免疫衰老与一种慢性全身性亚最佳炎症密切相关,称为炎症衰老(IFA),它通过改变ISC的动态(包括免疫系统随时间的加速变化)来破坏免疫耐受性的效率。因此,在MS期间,免疫耐受性可能会因IFA对ISC的不利定时影响而逐渐恶化。然而,迄今为止,尚无MS期间持续存在IFA的综合证据。本综述解决了这一限制,并通过评估与IFA相关的生物标志物研究,对有力证据进行了系统批判,以支持MS期间存在亚最佳炎症。这些发现为进一步明确证明MS中的IFA并深入了解该疾病的复杂病理和发展中的流行病学提供了依据。