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).
Objective:
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.
Methods:
We analyzed OPN plasma levels in 492 consecutive MS patients, using a commercial enzyme-linked immunosorbent assay (ELISA).
Results:
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.
Conclusion:
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.
MartinRBielekovaBHohlfeldR. Biomarkers in multiple sclerosis. Dis Markers2006; 22: 183–185.
2.
HarrisVKSadiqSA. Disease biomarkers in multiple sclerosis: Potential for use in therapeutic decision making. Molec Diag Ther2009; 13: 225–244.
3.
PepeMSFengZJanesH. Pivotal evaluation of the accuracy of a biomarker used for classification or prediction: Standards for study design. J Nat Can Inst2008; 100: 1432–1438.
4.
SteinmanL. A molecular trio in relapse and remission in multiple sclerosis. Nature Rev Immunol2009; 9: 440–447.
5.
ChabasDBaranziniSEMitchellD. The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease. Science2001; 294: 1731–1735.
BörnsenLKhademiMOlssonT. Osteopontin concentrations are increased in cerebrospinal fluid during attacks of multiple sclerosis. Mult Scler2011; 17: 32–42.
8.
VogtMHLopatinskayaLSmitsM. Elevated osteopontin levels in active relapsing–remitting multiple sclerosis. Ann Neurol2003; 53: 819–822.
9.
VogtMHTen KateJDrentRJ. Increased osteopontin plasma levels in multiple sclerosis patients correlate with bone-specific markers. Mult Scler2010; 16: 443–449.
10.
VogtMHFlorisSKillesteinJ. Osteopontin levels and increased disease activity in relapsing–remitting multiple sclerosis patients. J Neuroimmunol2004; 155: 155–160.
11.
GauthierSAGlanzBIMandelM. A model for the comprehensive investigation of a chronic autoimmune disease: The multiple sclerosis CLIMB study. Autoimmunity Rev2006; 5: 532–536.
12.
GauthierSAGlanzBIMandelM. Incidence and factors associated with treatment failure in the CLIMB multiple sclerosis cohort study. J Neurological Sci2009; 284: 116–119.
13.
KhademiMStolDOlssonT. Induction of systemic TNFalpha in natalizumab-treated multiple sclerosis. Eur J Neurol2008; 15: 309–312.
14.
NiinoMBodnerCSimardML. Natalizumab effects on immune cell responses in multiple sclerosis. Ann Neurol2006; 59: 748–754.
15.
KivisäkkPHealyBCVigliettaV. Natalizumab treatment in MS is associated with sequestration of proinflammatory T cells in peripheral blood. Neurology2009; 72: 1922–1930.
16.
BörnsenLChristensenJRRatzerR. Effect of natalizumab on circulating CD4+ T cells in multiple sclerosis. PLoS ONE2012; 7: e47578.
17.
De AndresCTeijeiroRAlonsoB. Long-term decrease in VLA-4 expression and functional impairment of dendritic cells during natalizumab therapy in patients with multiple sclerosis. PLoS ONE2012; 7: e34103.
18.
Begum-HaqueSChristyMWangY. Glatiramer acetate biases dendritic cells towards an anti-inflammatory phenotype by modulating OPN, IL-17 and RORgammat responses and by increasing IL-10 production in experimental allergic encephalomyelitis. J Neuroimmunol2013; 254: 117–124.
19.
RodriguesLRTeixeiraJASchmittFL. The role of osteopontin in tumor progression and metastasis in breast cancer. Cancer Epidemiol Biomark Prevent2007; 16: 1087–1097.
20.
SodekJBatistaDaSilvaAPZoharR. Osteopontin and mucosal protection. J Dental Res2006; 85: 404–415.
21.
BraitchMNunanRNiepelG. Increased osteopontin levels in the cerebrospinal fluid of patients with multiple sclerosis. Arch Neurol2008; 65: 633–635.
22.
ChowdhurySALinJSadiqSA. Specificity and correlation with disease activity of cerebrospinal fluid osteopontin levels in patients with multiple sclerosis. Arch Neurol2008; 65: 232–235.
23.
BrownLFPapadopoulos-SergiouABerseB. Osteopontin expression and distribution in human carcinomas. Am J Pathol1994; 145: 610–623.
24.
SengerDRPerruzziCAGraceyCF. Secreted phosphoproteins associated with neoplastic transformation: Close homology with plasma proteins cleaved during blood coagulation. Cancer Res1988; 48: 5770–5774.
25.
SennelsHSorensenSOstergaardM. Circulating levels of osteopontin, osteoprotegerin, total soluble receptor activator of nuclear factor-kappa B ligand, and high-sensitivity C-reactive protein in patients with active rheumatoid arthritis randomized to etanercept alone or in combination with methotrexate. Scand J Rheumatol2008; 37: 241–247.
26.
MasiLRicciLZulianF. Serum osteopontin as a predictive marker of responsiveness to methotrexate in juvenile idiopathic arthritis. J Rheumatol2009; 36: 2308–2313.
27.
SamitasKZervasEVittorakisS. Osteopontin expression and relation to disease severity in human asthma. Eur Resp J2011; 37: 331–341.
28.
ChenYJShenJLWuCY. Elevated plasma osteopontin level is associated with occurrence of psoriasis and is an unfavorable cardiovascular risk factor in patients with psoriasis. J Am Acad Dermatol2009; 60: 225–230.
29.
StepienEWypasekEStopyraK. Increased levels of bone remodeling biomarkers (osteoprotegerin and osteopontin) in hypertensive individuals. Clin Biochem2011; 44: 826–831.
30.
OhmoriRMomiyamaYTaniguchiH. Plasma osteopontin levels are associated with the presence and extent of coronary artery disease. Atherosclerosis2003; 170: 333–337.
31.
WallerAHSanchez-RossMKaluskiE. Osteopontin in cardiovascular disease: A potential therapeutic target. Cardiol Rev2010; 18: 125–131.
32.
BishopETheophilusEHFearonIM. In vitro and clinical studies examining the expression of osteopontin in cigarette smoke-exposed endothelial cells and cigarette smokers. BMC Cardiovasc Disord2012; 12: 75.
33.
SzalardyLZadoriDSimuM. Evaluating biomarkers of neuronal degeneration and neuroinflammation in CSF of patients with multiple sclerosis-osteopontin as a potential marker of clinical severity. J Neurolog Sci2013; 331: 38–42.
