Biomarkers in Multiple Sclerosis: An Up-to-Date Overview

Abstract

During the last decades, the effort of establishing satisfactory biomarkers for multiple sclerosis has been proven to be very difficult, due to the clinical and pathophysiological complexities of the disease. Recent knowledge acquired in the domains of genomics-immunogenetics and neuroimmunology, as well as the evolution in neuroimaging, has provided a whole new list of biomarkers. This variety, though, leads inevitably to confusion in the effort of decision making concerning strategic and individualized therapeutics. In this paper, our primary goal is to provide the reader with a list of the most important characteristics that a biomarker must possess in order to be considered as reliable. Additionally, up-to-date biomarkers are further divided into three subgroups, genetic-immunogenetic, laboratorial, and imaging. The most important representatives of each category are presented in the text and for the first time in a summarizing workable table, in a critical way, estimating their diagnostic potential and their efficacy to correlate with phenotypical expression, neuroinflammation, neurodegeneration, disability, and therapeutical response. Special attention is given to the “gold standards” of each category, like HLA-DRB1∗ polymorphisms, oligoclonal bands, vitamin D, and conventional and nonconventional imaging techniques. Moreover, not adequately established but quite promising, recently characterized biomarkers, like TOB-1 polymorphisms, are further discussed.

HLA-DRB1* Allele Frequencies in Pediatric, Adolescent and Adult-Onset Multiple Sclerosis Patients, in a Hellenic Sample. Evidence for New and Established Associations

“…Both environmental and genetic factors have been implicated in the pathogenesis of the disease leading to the well-known consideration of MS as a complex multi-factorial disease entity [1]. Concerning genetics, linkage studies in many populations consistently have showed that the human leukocyte antigens (HLA), products of the Major Histocompatibility Complex (MHC) on chromosome 6p21.3 are linked to MS [1,2]. MHC represents a cluster of highly polymorphic genes, including the HLA-Class I, II and III genes that encode proteins which serve antigen presentation to T-lymphocytes.…”

Interleukin-33 plasma levels in patients with relapsing-remitting multiple sclerosis

“…Cytokines have various functions in health and diseases, especially in MS (13)(14)(15)(16). One of the most important cytokines that directly contributes to the immunopathogenesis of MS is IL-33 (17), a recently discovered cytokine, taking part in various inflammatory and autoimmune diseases like psoriasis, lupus erythematous, ulcerative colitis and MS (17)(18)(19)(20).…”

Evidence of disease control: a realistic concept beyond NEDA in the treatment of multiple sclerosis

“…The determination of biomarkers of inflammation and neurodegeneration in body fluids, combined with the use of non-conventional MRI with the ability to detect changes in the normal appearing brain tissue, could assist in the detection of a sequence of cellular and molecular events, inside and out of the CNS, that occur before fulfilling the current definition of NEDA composite. Multiple biomarkers have been identified in MS, but their validation and clinical application have not been established 7, 8 . Teunissen recently discussed the use of biomarkers for MS such as N-acetylaspartate (representing mitochondrial dysfunction and/or neuro-axonal loss), chitinase 3 like-protein 1 (meaning reactive astrogliosis and microglial activity), neurofilament light chain (related to axonal loss) and glial fibrillary acidic protein (representing astrocytic cytoskeleton injury).…”