Identification of Biomarkers in Cerebrospinal Fluid and Serum of Multiple Sclerosis Patients by Immunoproteomics Approach

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2014 Dec 18

PMID 25517032

Citations 5

Authors

Paolo Colomba

Simona Fontana

Giuseppe Salemi

Marilisa Barranca

Claudia Lo Sicco

Maria Antonietta Mazzola

Paolo Ragonese

Giovanni Savettieri

Giacomo De Leo

Riccardo Alessandro

Giovanni Duro

Affiliations

Soon will be listed here.

Abstract

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system. At present, the molecular mechanisms causing the initiation, development and progression of MS are poorly understood, and no reliable proteinaceous disease markers are available. In this study, we used an immunoproteomics approach to identify autoreactive antibodies in the cerebrospinal fluid of MS patients to use as candidate markers with potential diagnostic value. We identified an autoreactive anti-transferrin antibody that may have a potential link with the development and progression of MS. We found this antibody at high levels also in the serum of MS patients and created an immunoenzymatic assay to detect it. Because of the complexity and heterogeneity of multiple sclerosis, it is difficult to find a single marker for all of the processes involved in the origin and progression of the disease, so the development of a panel of biomarkers is desirable, and anti-transferrin antibody could be one of these.

Citing Articles

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References

Zeman D, Adam P, Kalistova H, Sobek O, Kelbich P, Andel J . Transferrin in patients with multiple sclerosis: a comparison among various subgroups of multiple sclerosis patients. Acta Neurol Scand. 2000; 101(2):89-94. DOI: 10.1034/j.1600-0404.2000.101002089.x. View

Coutinho A, Kazatchkine M, Avrameas S . Natural autoantibodies. Curr Opin Immunol. 1995; 7(6):812-8. DOI: 10.1016/0952-7915(95)80053-0. View

Silber E, Semra Y, Gregson N, Sharief M . Patients with progressive multiple sclerosis have elevated antibodies to neurofilament subunit. Neurology. 2002; 58(9):1372-81. DOI: 10.1212/wnl.58.9.1372. View

Eikelenboom M, Petzold A, Lazeron R, Silber E, Sharief M, Thompson E . Multiple sclerosis: Neurofilament light chain antibodies are correlated to cerebral atrophy. Neurology. 2003; 60(2):219-23. DOI: 10.1212/01.wnl.0000041496.58127.e3. View

Berger T, Rubner P, Schautzer F, Egg R, Ulmer H, Mayringer I . Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event. N Engl J Med. 2003; 349(2):139-45. DOI: 10.1056/NEJMoa022328. View

Burdo J, Antonetti D, Wolpert E, Connor J . Mechanisms and regulation of transferrin and iron transport in a model blood-brain barrier system. Neuroscience. 2003; 121(4):883-90. DOI: 10.1016/s0306-4522(03)00590-6. View

Lefranc D, Almeras L, Dubucquoi S, De Seze J, Vermersch P, Prin L . Distortion of the self-reactive IgG antibody repertoire in multiple sclerosis as a new diagnostic tool. J Immunol. 2003; 172(1):669-78. DOI: 10.4049/jimmunol.172.1.669. View

Quintana F, Cohen I . The natural autoantibody repertoire and autoimmune disease. Biomed Pharmacother. 2004; 58(5):276-81. DOI: 10.1016/j.biopha.2004.04.011. View

Walsh M, Murray J . Dual implication of 2',3'-cyclic nucleotide 3' phosphodiesterase as major autoantigen and C3 complement-binding protein in the pathogenesis of multiple sclerosis. J Clin Invest. 1998; 101(9):1923-31. PMC: 508779. DOI: 10.1172/JCI1983. View

10.

Lacroix-Desmazes S, Kaveri S, Mouthon L, Ayouba A, Malanchere E, Coutinho A . Self-reactive antibodies (natural autoantibodies) in healthy individuals. J Immunol Methods. 1998; 216(1-2):117-37. DOI: 10.1016/s0022-1759(98)00074-x. View

11.

Genain C, Cannella B, Hauser S, Raine C . Identification of autoantibodies associated with myelin damage in multiple sclerosis. Nat Med. 1999; 5(2):170-5. DOI: 10.1038/5532. View

12.

Levine S, Lynch S, Ou C, Wulser M, Tam E, Boo N . Ferritin, transferrin and iron concentrations in the cerebrospinal fluid of multiple sclerosis patients. Brain Res. 1999; 821(2):511-5. DOI: 10.1016/s0006-8993(98)01360-2. View

13.

Sospedra M, Martin R . Immunology of multiple sclerosis. Annu Rev Immunol. 2005; 23:683-747. DOI: 10.1146/annurev.immunol.23.021704.115707. View

14.

Roxburgh R, Seaman S, Masterman T, Hensiek A, Sawcer S, Vukusic S . Multiple Sclerosis Severity Score: using disability and disease duration to rate disease severity. Neurology. 2005; 64(7):1144-51. DOI: 10.1212/01.WNL.0000156155.19270.F8. View

15.

Freedman M, Thompson E, Deisenhammer F, Giovannoni G, Grimsley G, Keir G . Recommended standard of cerebrospinal fluid analysis in the diagnosis of multiple sclerosis: a consensus statement. Arch Neurol. 2005; 62(6):865-70. DOI: 10.1001/archneur.62.6.865. View

16.

Lolli F, Mulinacci B, Carotenuto A, Bonetti B, Sabatino G, Mazzanti B . An N-glucosylated peptide detecting disease-specific autoantibodies, biomarkers of multiple sclerosis. Proc Natl Acad Sci U S A. 2005; 102(29):10273-8. PMC: 1177382. DOI: 10.1073/pnas.0503178102. View

17.

Cid C, Alvarez-Cermeno J, Salinas M, Alcazar A . Anti-heat shock protein 90beta antibodies decrease pre-oligodendrocyte population in perinatal and adult cell cultures. Implications for remyelination in multiple sclerosis. J Neurochem. 2005; 95(2):349-60. DOI: 10.1111/j.1471-4159.2005.03371.x. View

18.

Reindl M, Khalil M, Berger T . Antibodies as biological markers for pathophysiological processes in MS. J Neuroimmunol. 2006; 180(1-2):50-62. DOI: 10.1016/j.jneuroim.2006.06.028. View

19.

McFarland H, Martin R . Multiple sclerosis: a complicated picture of autoimmunity. Nat Immunol. 2007; 8(9):913-9. DOI: 10.1038/ni1507. View

20.

Mathey E, Derfuss T, Storch M, Williams K, Hales K, Woolley D . Neurofascin as a novel target for autoantibody-mediated axonal injury. J Exp Med. 2007; 204(10):2363-72. PMC: 2118456. DOI: 10.1084/jem.20071053. View