Abstract
Identifying a reliable biomarker may accelerate diagnosis of multiple sclerosis (MS) and lead to early management of the disease. Accumulating evidence suggest that cerebrospinal fluid (CSF) and peripheral blood concentration of osteopontin (OPN) may have diagnostic and prognostic value in MS. We conducted a systematic review and meta-analysis of studies that measured peripheral blood and CSF levels of OPN in MS patients and controls to evaluate the diagnostic potential of this biomarker better. We searched PubMed, Web of Science and Scopus databases to find articles that measured OPN concentration in peripheral blood and CSF samples from MS patients up to October 19, 2016. Q statistic tests and the I2 index were applied for heterogeneity assessment. If the I2 index was less than 40%, the fixed-effects model was used for meta-analysis. Random-effects meta-analysis was chosen if the I2 value was greater than 40%. After removal of duplicates, 918 articles were identified, and 27 of them fulfilled the inclusion criteria. We included 22 eligible studies in the final meta-analysis. MS patients, in general, had considerably higher levels of OPN in their CSF and blood when compared to all types of controls (p<0.05). When the comparisons were made between different subtypes of MS patients and controls, the results pointed to significantly higher levels of OPN in CSF of MS subgroups (p<0.05). All subtypes of MS patients, except CIS patients, had increased blood levels of OPN compared to controls (p<0.05). In the second set of meta-analyses, we compared the peripheral blood and CSF concentrations of OPN between MS patient subtypes. CIS patients had significantly lower levels of OPN both in their peripheral blood and CSF compared to patients with progressive subtypes of MS (p<0.05). CSF concentration of OPN was significantly higher among RRMS patients compared to the CIS patients and SPMS patients (P<0.05). Finally, patients with active MS had significantly higher OPN levels in their CSF compared to patients with stable disease (P = 0.007). The result of this study confirms that increased levels of OPN exist in CSF and peripheral blood of MS patients and strengthens the evidence regarding the clinical utility of OPN as a promising and validated biomarker for MS.
Highlights
Multiple sclerosis is a chronic, progressive, immune-mediated central nervous system (CNS) disorder characterized by inflammation, demyelination and axonal damage leading to neurodegeneration [1]
According to their clinical course, multiple sclerosis (MS) patients are categorized into four major subtypes: (1) clinically isolated syndrome (CIS); an initial presentation of MS, (2) relapsing-remitting MS (RRMS); the most common type of MS, (3) primary progressive MS (PPMS); clinically progressive disease without any recovery, and (4) secondary progressive MS (SPMS); which usually develops after years of relapsingremitting disease [3]
The results of this study indicate that both peripheral blood and cerebrospinal fluid (CSF) levels of this biomarker are increased among MS patients
Summary
Multiple sclerosis is a chronic, progressive, immune-mediated central nervous system (CNS) disorder characterized by inflammation, demyelination and axonal damage leading to neurodegeneration [1]. MS affects more than 2.5 million people worldwide [2], and is a leading cause of disability in young adults. According to their clinical course, MS patients are categorized into four major subtypes: (1) clinically isolated syndrome (CIS); an initial presentation of MS, (2) relapsing-remitting MS (RRMS); the most common type of MS, (3) primary progressive MS (PPMS); clinically progressive disease without any recovery, and (4) secondary progressive MS (SPMS); which usually develops after years of relapsingremitting disease [3]. Since blood collection is a less invasive procedure, finding a reliable blood-borne biomarker for MS is urgently needed [5, 11, 12]
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