Body fluid biomarkers in multiple sclerosis: how far we have come and how they could affect the clinic now and in the future

Abstract

Multiple Sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS) which affects over 2.5 million people worldwide. Although MS has been extensively studied, many challenges still remain in regards to treatment, diagnosis, and prognosis. Typically, prognosis and individual responses to treatment are evaluated by clinical tests such the expanded disability status scale (EDSS), magnetic resonance imaging (MRI), and presence of oligoclonal bands (OCB) in the cerebrospinal fluid (CSF). However, none of these measures correlate strongly with treatment efficacy or disease progression across heterogeneous patient populations and subtypes of MS. Numerous studies over the past decades have attempted to identify sensitive and specific biomarkers for diagnosis, prognosis, and treatment efficacy of MS. The objective of this article is to review and discuss the current literature on body fluid biomarkers in MS, including research on potential biomarker candidates in the areas of microRNA, messenger RNA, lipids, and proteins.

The physiology of blood platelets and changes of their biological activities in multiple sclerosis

“…Moreover, platelets can release many factors following heterotypical intercellular aggregation or adherence to leukocytes. Among the most potent inflammatory signaling molecules secreted by platelets are chemokines (Table I): RANTES (CCL5) binding inflamed endothelium, CXCL5, CCL3 and PF4 (CXCL4) (Raphael et al 2015). The mediators released from platelet granules, specially adhesive proteins, growth factors, chemokines important in hemostasis, may be implicated together with MMPs in the progression of inflammatory process (Morrell et al 2014) and facilitates the involvement of platelets in acute chronic inflammatory diseases (Müller et al 2015).…”

“…Moreover, platelets exert influence on inflammation by release of pro-inflammatory and immune-modulating factors. A wide range of chemokines including CXCL1, CXCL4, CXCL5 (ENA-78, epithelial neutrophil-activating protein 78), CXCL7 (PBP, B-TG, CTAP-III, NAP-2), CXCL8 (IL-8), CXCL12, CCL2, CCL3 (MIP-1α, macrophage inflammatory protein-1α), CCL5 (RANTES) ( Table I), are stored in platelet α-granules (Raphael et al 2015). Among these chemokines CXCL4 and CXCL7 are the abundant.…”

Autologous Bone Marrow Transplantation in Multiple Sclerosis: Biomarker Relevance for Patient Recruitment and Follow up

“…The application of a method that would give significant priority to the use of specific biomarkers of inflammation and degeneration, as predictors of disease progression and response to therapy, will result in better patient selection for AHSCT thus improving prognosis. Patients who carry the HLA-DRB1*15:01 allele have shown positive correlation with oligoclonal bands (OCB) in CSF, early disease onset, risk of cognitive decline, presence of bigger white matter lesions, more advanced brain atrophy, higher lesion load on MRI, and higher concentration of matrix metalloproteinase-9 (MMP-9) in CSF [23,24]. T-cells and activated monocytes and macrophages have the ability to produce a variety of matrix metalloproteinases, including MMP-9, which cause degradation of the extracellular matrix and facilitate migration of leucocytes through the basement membranes [25].…”

Oxidative Stress-Related Biomarkers in Multiple Sclerosis: A Review

“…Individual markers of high predictive value are seldom identified, and the physiological implications are frequently unclear. MicroRNAs, small non-coding RNAs which regulate posttranscriptional gene expression, are an emerging group of micromolecules with potential as biomarkers in MS [6].…”