Relapsing/remitting multiple sclerosis: A speculative model and its implications for a novel treatment

Abstract

AbstractThe 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.