Oxidative stress plays an important role in multiple sclerosis (MS). Isoprostanes are biomarkers for oxidative stress and have been related to neurological disease progression.
Objective:
To study whether plasma isoprostane levels were related to disease progression in MS.
Methods:
Plasma levels of 8,12-iso-iPF2alpha-VI were determined in 17 patients with clinically isolated syndrome (CIS), 41 relapsing–remitting MS (RRMS) patients and 5 primary progressive MS (PPMS) patients and related to MRI and clinical disease parameters.
Results:
Isoprostane levels were similar in CIS (60.9, interquartile range (IQR): 47.7–77.7 pg/ml) and RRMS patients (65.3, IQR: 51.9–82.8 pg/ml). The plasma levels were lower in PPMS patients (42.5, IQR: 37.1–49.9) pg/ml, p<0.05) compared to CIS and RRMS patients in this cohort, which was not confirmed in a second cohort. Baseline isoprostane levels were not related to clinical progression defined by conversion form CIS to RRMS or change in Expanded Disability Status Scale (EDSS) or MS Functional Composite (MSFC) scores during six years of follow-up (CIS + RRMS), nor to change in volume of gadolinium enhancing lesions, T2 lesion load or T1 hypointense lesion load during 2.8 years of follow-up (CIS + RRMS).
Conclusion:
These results do not support a strong role of 8,12-iso-iPF2alpha-VI in the prediction of disease progression in MS.
BitschASchuchardtJBunkowskiS, et al. Acute axonal injury in multiple sclerosis. Correlation with demyelination and inflammation. Brain2000; 123: 1174–1183.
2.
BöLDawsonTMWesselinghS, et al. Induction of nitric oxide synthase in demyelinating regions of multiple sclerosis brains. Ann Neurol1994; 36: 778–786.
3.
Van HorssenJSchreibeltGBoL, et al. NAD(P)H: quinone oxidoreductase 1 expression in multiple sclerosis lesions. Free Radic Biol Med2006; 41: 311–317.
4.
SmithKJKapoorRHallSM, et al. Electrically active axons degenerate when exposed to nitric oxide. Ann Neurol2001; 49: 470–476.
5.
QiXLewinASSunL, et al. Mitochondrial protein nitration primes neurodegeneration in experimental autoimmune encephalomyelitis. J Biol Chem2006; 281: 31950–62.
6.
BeslerHTComogluSOkcuZ. Serum levels of antioxidant vitamins and lipid peroxidation in multiple sclerosis. Nutr Neurosci2002; 5: 215–220.
7.
BeslerHTComogluS. Lipoprotein oxidation, plasma total antioxidant capacity and homocysteine level in patients with multiple sclerosis. Nutr Neurosci2003; 6: 189–196.
8.
RistoriGBrescianiniSPinoA, et al. Serum elements and oxidative status in clinically isolated syndromes: imbalance and predictivity. Neurology2011; 76: 549–555.
9.
FerrettiGBacchettiTPrincipiF, et al. Increased levels of lipid hydroperoxides in plasma of patients with multiple sclerosis: a relationship with paraoxonase activity. Mult Scler2005; 11: 677–682.
10.
KochMMostertJArutjunyanAV, et al. Plasma lipid peroxidation and progression of disability in multiple sclerosis. Eur J Neurol2007; 14: 529–533.
11.
GrecoAMinghettiLSetteG, et al. Cerebrospinal fluid isoprostane shows oxidative stress in patients with multiple sclerosis. Neurology1999; 53: 1876–1879.
12.
GrecoAMinghettiLPuopoloM, et al. Cerebrospinal fluid isoprostanes are not related to inflammatory activity in relapsing-remitting multiple sclerosis. J Neurol Sci2004; 224: 23–27.
13.
MillerEMrowickaMSaluk-JuszczakJ, et al. The level of isoprostanes as a non-invasive marker for in vivo lipid peroxidation in secondary progressive multiple sclerosis. Neurochem Res2011; 36: 1012–6.
14.
MattssonNHaghighiSAndersenO, et al. Elevated cerebrospinal fluid F2-isoprostane levels indicating oxidative stress in healthy siblings of multiple sclerosis patients. Neurosci Lett2007; 414: 233–236.
15.
De LeonMJDeSantiSZinkowskiR, et al. Longitudinal CSF and MRI biomarkers improve the diagnosis of mild cognitive impairment. Neurobiol Aging2006; 27: 394–401.
16.
PraticoDClarkCMLiunF, et al. Increase of brain oxidative stress in mild cognitive impairment: a possible predictor of Alzheimer disease. Arch Neurol2002; 59: 972–976.
17.
KesterMISchefferPGKoel-SimmelinkMJ, et al. Serial CSF sampling in Alzheimer’s disease: specific versus non-specific markers. Neurobiol Aging2011.
18.
MillerDBarkhofFMontalbanX, et al. Clinically isolated syndromes suggestive of multiple sclerosis, part 2: non-conventional MRI, recovery processes, and management. Lancet Neurol2005; 4: 341–348.
19.
BruckWLucchinettiCLassmannH. The pathology of primary progressive multiple sclerosis. Mult Scler2002; 8: 93–97.
20.
PoserCMPatyDWScheinbergL, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol1983; 13: 227–231.
21.
BarkhofFFilippiMMillerDH, et al. Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis. Brain1997; 120: 2059–2069.
22.
CutterGRBaierMLRudickRA, et al. Development of a multiple sclerosis functional composite as a clinical trial outcome measure. Brain1999; 122: 871–82.
23.
KurtzkeJF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology1983; 33: 1444–1452.
24.
TeunissenCEPetzoldABennettJL, et al. A consensus protocol for the standardization of cerebrospinal fluid collection and biobanking. Neurology2009; 73: 1914–1922.
25.
LublinFDReingoldSC. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology1996; 46: 907–911.
26.
QinYDuquettePZhangY, et al. Intrathecal B-cell clonal expansion, an early sign of humoral immunity, in the cerebrospinal fluid of patients with clinically isolated syndrome suggestive of multiple sclerosis. Lab Invest2003; 83: 1081–1088.
27.
BergerTRubnerPSchautzerF, et al. Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event. N Engl J Med2003; 349: 139–145.
28.
LimETBergerTReindlM, et al. Anti-myelin antibodies do not allow earlier diagnosis of multiple sclerosis. Mult Scler2005; 11: 492–494.
29.
TumaniHLehmensiekVRauD, et al. CSF proteome analysis in clinically isolated syndrome (CIS): candidate markers for conversion to definite multiple sclerosis. Neurosci Lett2009; 452: 214–217.
30.
ComabellaMMontalbanXKakalachevaK, et al. B cell expression of the inhibitory Fc gamma receptor is unchanged in early MS. J Neuroimmunol2010; 223: 135–137.
31.
BrettschneiderJCzerwoniakASenelM, et al. The chemokine CXCL13 is a prognostic marker in clinically isolated syndrome (CIS). PLoS One2010; 5: e11986.
32.
RistoriGBrescianiniSPinoA, et al. Serum elements and oxidative status in clinically isolated syndromes: imbalance and predictivity. Neurology2011; 76: 549–555.
33.
MillerDBarkhofFMontalbanX, et al. Clinically isolated syndromes suggestive of multiple sclerosis, part I: natural history, pathogenesis, diagnosis, and prognosis. Lancet Neurol2005; 4: 281–288.
34.
MufsonEJLeurgansS. Inability of plasma and urine F2A-isoprostane levels to differentiate mild cognitive impairment from Alzheimer’s disease. Neurodegener Dis2010; 7: 139–142.
35.
IrizarryMCYaoYHymanBT, et al. Plasma F2A isoprostane levels in Alzheimer’s and Parkinson’s disease. Neurodegener Dis2007; 4: 403–405.
