Evaluation of circulating osteopontin levels in an unselected cohort of patients with multiple sclerosis: relevance for biomarker development
ABSTRACT Osteopontin (OPN) is a pleiotropic protein with important roles in inflammation and immunity that has been suggested as a candidate biomarker for disease activity in multiple sclerosis (MS).
We evaluated plasma levels of OPN in an unselected cohort of MS patients, to determine its potential as a biomarker for disease subtype and/or disease activity in a regular clinical setting.
We analyzed OPN plasma levels in 492 consecutive MS patients, using a commercial enzyme-linked immunosorbent assay (ELISA).
OPN levels were higher in relapsing-remitting and secondary progressive MS, compared to healthy controls. Treatment with natalizumab or glatiramer acetate was associated with lower OPN levels. There was no significant association between the OPN levels and disease activity, as measured by clinical or radiological criteria. One-third of patients with high OPN levels had concurrent disorders that may also be associated with increased OPN expression, and which may mask a modest effect of MS disease activity on OPN levels.
Our data do not support a role for circulating OPN levels as a biomarker for disease activity in a heterogeneous clinical setting, but does not rule out a potential role in the cerebrospinal fluid, in a controlled setting such as a clinical trial, or in concert with other biomarkers.
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ABSTRACT: Multiple sclerosis (MS) is a neuroimmunological disorder characterized by central nervous system demyelination, axonal injury and loss. Considering the complexity of its aetiopathogenesis, early diagnosis of MS and individualized management are challenging in clinical practice. As the pathophysiologic and pharmacological indicators, studies on biomarkers in MS are useful for early prediction and diagnosis, monitoring of disease activity and predicting treatment response. In this review, we will summarize recent development of biomarker studies in MS from protein molecules to noncoding RNAs.Neurochemical Research 07/2014; 39(9). DOI:10.1007/s11064-014-1386-z · 2.55 Impact Factor
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ABSTRACT: Multiple sclerosis (MS) is an autoimmune disease of unknown cause, in which chronic inflammation drives multifocal demyelination of axons in both white and gray matter in the CNS. The pathological course of the disease is heterogeneous and involves an early, predominantly inflammatory demyelinating disease phase of relapsing-remitting MS (RRMS), which, over a variable period of time, evolves into a progressively degenerative stage associated with axonal loss and scar formation, causing physical and cognitive disability. For patients with RRMS, there is a growing arsenal of disease-modifying agents (DMAs), with varying degrees of efficacy, as defined by reduced relapse rates, improved magnetic resonance imaging outcomes, and preservation of neurological function. Establishment of personalized treatment plans remains one of the biggest challenges in therapeutic decision-making in MS because the disease prognosis and individual therapeutic outcomes are extremely difficult to predict. Current research is aimed at discovery and validation of biomarkers that reliably measure disease progression and effective therapeutic intervention. Individual biomarker candidates with evident clinical utility are highlighted in this review and include neutralizing autoantibodies against DMAs, fetuin-A, osteopontin, isoprostanes, chemokine (C-X-C motif) ligand 13 (CXCL13), neurofilament light and heavy, and chitinase 3-like protein. In addition, application of more advanced screening technologies has opened up new categories of biomarkers that move beyond detection of individual soluble proteins, including gene expression and autoantibody arrays, microRNAs, and circulating microvesicles/exosomes. Development of clinically useful biomarkers in MS will not only shape the practice of personalized medicine but will also serve as surrogate markers to enable investigation of innovative treatments within clinical trials that are less costly, are of shorter duration, and have more certainty of outcomes.Molecular Diagnosis & Therapy 08/2014; 18(6). DOI:10.1007/s40291-014-0117-0 · 2.59 Impact Factor
Article: Developing Biomarkers for MS.[Show abstract] [Hide abstract]
ABSTRACT: Existing clinical outcomes of disease activity, including relapse rates, are inherently insensitive to the underlying pathological process in MS. Moreover, it is extremely difficult to measure clinical disability in patients, which is often a retrospective assessment, and definitely not within the time frame of a clinical trial. BiomarkersBiomarkers , conversely are more specific for a pathologic process and if used correctly can prove invaluable in the diagnosis, stratification and monitoring of disease activity, including any subclinical activity which is not visible to the naked eye. In this chapter, we discuss the development of neurofilamentsNeurofilaments as surrogate outcomes of disability in MS. The validationValidation and qualificationQualification are vital steps in biomarkerBiomarker development and to gaining acceptance in scientific community, and the pitfalls leading up to this are also discussed.