Innate immunity and biomarkers of multiple sclerosis relapse versus remission

Multiple sclerosis (MS) is a neurodegenerative and inflammatory disease presenting most commonly in its relapsing and remitting form, whereby a relapse is defined as an acute exacerbation of disease activity associated with worsening disability. Relapse diagnosis is impeded by its heterogeneous presentation, limited detectability on magnetic resonance imaging and 'pseudo-relapse' which occurs due to factors unrelated to MS itself such as infection. Currently, we do not have easily accessible biomarkers that can distinguish relapse from remission. The diagnosis is generally made on clinical grounds as per the discretion of a neurologist and relapse treatment constitutes usage of high dose corticosteroids which may not provide long term benefit. Additionally, the recurrent usage of high dose corticosteroids is associated with a myriad of side effects and their mechanism of action is not targeted. To improve diagnostic and treatment strategies for MS relapse, we must first understand the underlying biology involved. Most literature in this field focuses on lymphocytes, overlooking innate immunity. Indeed, all the current disease modifying therapies in MS target lymphocytes. However, there is increasing evidence for the role of innate immune cells in MS disease activity. This review will discuss MS disease, relapse presentation, treatment strategies, the cellular composition of different lesion types and consider current biomarkers of disease activity versus disease stability. With a focus on innate immunity, we hope to provide new insight into future novel biomarkers to capture MS disease activity.