Prognostic significance of intrathecal oligoclonal immunoglobulin G in multiple sclerosis
Keywords:
Oligoclonal bands, Multiple sclerosis, Prognosis
Abstract
Introduction/Aim: Detection of intrathecal oligoclonal bands of immunoglobulin G (OB IgG), in addition to diagnostic, has a predictive significance in multiple sclerosis (MS). The aim of the study was to determine the prognostic significance of OB IgG and to correlate the presence of OB IgG with the progression of disability in MS patients.
Methods: A retrospective-prospective cohort study included 177 MS patients examined at the Centre for MS, Clinic of Neurology, University Clinical Centre of the Republic of Srpska. In all patients, demographic data, clinical parameters, Expanded Disability Status Scale (EDSS) score, isoelectric focusing (IEF) of cerebrospinal fluid (CSF), cyto-biochemical analysis of CSF, evoked potentials (EP) and magnetic resonance (MR) of the head were analysed. MS patients were divided in two groups: with and without intrathecal synthesis of oligoclonal IgG. According to the EDSS determined in both groups, the relation between the degree of functional disability and the presence of OB in the CSF and also with characteristics of the cyto-biochemical profile were analysed. Methods of descriptive and analytical statistics, analysis of variance, chi-square test, Bonferroni's post hoc test, correlation and regression analysis were used in the analysis of the results.
Results: In the examined cohort of MS patients, the sensitivity of IEF was 96.6 %. There was a statistically significant association between the detectability of intrathecally synthesised IgG and EDSS score (p = 0.004) so that individuals who do not have intrathecally synthesised IgG had lower EDSS scores. MS patients with a CSF protein concentration > 0.40 g/L were 2.45 times more likely to enter secondary progression and 2.51 times more likely to achieve EDSS 4.0.
Conclusion: IEF is a very sensitive diagnostic and prognostic method for MS patients, which indicates a more benign course of MS in patients without oligoclonal bands in the CSF.
References
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39. Drulović J. Terapija koja modifikuje prirodni tok multiple skleroze. U: Drulović J. Multipla skleroza. Medicinski fakultet Univerziteta u Beogradu 2013; 161-182.
40. Drulovic J, Cukic M, Grgic S, Dincic E, Raicevic R, Congor N et al. The Impact of Betaplus Program on patient treatment satisfaction with interferon beta-1b in multiple sclerosis: Multicenter cross-sectional survey in the Western Balkan countries. Mult Scler Relat Disord. 2016; 11: 56-61.
41. Yadav SK, Mindur JE, Ito K, Dhib-Jalbut S. Advances in the immunopathogenesis of multiple sclerosis. Curr Opin Neurol. 2015;28:206–19.
42. Ontaneda D, Fox RJ. Progressive multiple sclerosis. Curr Opin Neurol. 2015;28:237–43.
43. Lanza CV, Bramanti P, Mazzon E et al. Biomarkers identification for PML monitoring, during Natalizumab (Tysabri®) treatment in Relapsing-Remitting Multiple Sclerosis. Mult Scler Relat Disord. 2018;20:93-99.
44. Autor, 2014.
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46. Dominques RB et all. The cerebrospinal fluid in multiple sclerosis: far beyond the bands. Einstein. 2017.;15(1):100-104.
47. Brändle SM, Obermeier B, Senel M. et al. Distinct oligoclonal band antibodies in multiple sclerosis recognize ubiquitous self-proteins.PNAS. 2016; 113(28) 7864-7869
48. Mc Nicholas N, Hutchinson M, McGuigan C, Chataway J. 2017 McDonald diagnostic criteria: A review of the evidence. Mult Scler Rel Disord. 2018; 24:48-54.
49. Arrambide G et al. The value of oligoclonal bands in the multiple sclerosis diagnostic criteria. Brain. 2018; 141(4): 1-10.
50. Frau J, Villar LM, Sardu C, Secci MA, Schirru L, Ferraro D et al. Intrathecal oligoclonal bands synthesis in multiple sclerosis: is it always a prognostic factor? J Neurol. 2018; 265(2):424-430.
51. Sun X, Bakhti M, Fitzner D et al. Quantified CSF antibody reactivity against myelin in multiple sclerosis. Ann Clin Transl Neurol. 2015; 2(12):1116–1123.
52. Katsavos S, Anagnostouli M. Biomarkers in Multiple Sclerosis: An Up-to-Date Overview. Mult Scler Int. 2013; 2013: 340-508.
53. Kuhle J, Disanto G, Dobson R, Adiutori R, Bianchi I, Topping J et al. Conversion from clinically isolated syndrome to multiple sclerosis: A large multicenter study. MSJ 2015; 21(8):1 013–24.
54. Huang WJ, Chen WW, Zhang X. Multiple sclerosis: Pathology, diagnosis and treatments. Exp Ther Med. 2017; 13(6): 3163–3166.
2. Autor, 2013.
3. Drulović J. Analiza oligoklonalnog imunoglobulina G u diferencijalnoj dijagnozi neuroloških obolenja. Medicinski fakultet Univerziteta u Beogradu, doktorska disertacija, 1994.
4. Rolas JI, Patricco TS, Cristiana E. Oligoclonal bands in multiple sclerosis patients: worse prognosis. Neurol Res 2012;34(9):889-892.
5. Drulović J, Stojisavljević N, Dujmović. Findings of cerebrospinal fluid in the diagnosis of multiple scleorosis. Srp Arh Celok Lek 1995; 123: 7-8.
6. Dell Avvento S, Sotgio MA, Mance S, Sotgiu G, Sotgiu S. Epidemiology of multiple sclerosids in the pediatric population of Sardinia, Italy. Eur J Pediatr. 2016; 175(1): 19-21.
7. Waldman A, Ghezzi A, Bar-Or A, Mikaeloff Y, Tardieu m, Banwell B. Multiple sclerosis in children: an update on clinical diagnosis therapeutic strategies, and research. Lancet Neurol. 2014; 13(9): 936-948.
8. Ghasemi N, Razavi S, Nikzad E. Multiple Sclerosis: Pathogenesis, Symptoms, Diagnosis and Cell-Based Therapy. Cell J 2017; 19(1): 1-10.
9. Holloman JP, Ho CC, Hukki A, Huntley JL, Gallicano GI. The development of hematopoietic and mesenchymal stem cell transplantation as an effective treatment for multiple sclerosis. Am J Stem Cells. 2013;2(2):95–107.
10. Gelfand JM. Multiple sclerosis: diagnosis, differential diagnosis, and clinical presentation. Handb Clin Neurol. 2014;122:269–290.
11. Fredrikson S. Clinical usefulness of cerebrospinal fluid evaluation. Intern Mult Scler J. 2010;17:24-27.
12. Dutta R, Trapp BD. Relapsing and progressive forms of multiple sclerosis – insights from pathology. Curr Opin Neurol. 2014; 27(3). 271-278.
13. Miller DH, Chard DT,Cicconelli O.Clinically isolated syndromes. Lancet Neurol 2012;11:157-169.
14. Dujmovic BI, Drulović J, Pekmezovic T. Prirodni tok i prognoza multiple skleroze. U: Drulović J. Multipla skleroza. Medicinski fakultet Univerziteta u Beogradu 2013; 32-46.
15. Lublin FD, Reingold CS, Cohen AJ, Cutter RG, Sorenson PS. Defining the clinical course of multiple sclerosis: he 2013. revisions. Neurology. 2014; 83(3): 278-286.
16. Stangel M, Fredrikson S, Meinl E, Petzold E. The utility of cerebrospinal fluid analysis in patients with multiple sclerosis. Nat Rev Neurol 2013;10:41.
17. Lublin FD. New multiple sclerosis phenotypic classification. Eur Neurol. 2014; 72(1):1-5.
18. Kale N. Optic neuritis as an early sign of multiple sclerosis. Eye Brain. 2016; 8: 195-202.
19. Adam MK, Krespan K, Moster ML, Serott RC. Simultaneous, Bilateral Ophthalmoplegia as the Presenting Sign of Paediatric Multiple Sclerosis: Case Report and Discussion of the Differential Diagnosis. Neuroophtalmology. 2014; 38(4): 230-237.
20. Avasarala JP, Cross AH, Trotter JL. Oligoclonal band number as a marker for prognosis in multiple sclerosis. Arch Neurol 2001;18:2044-2046.
21. Rolas JI, Patricco TS, Cristiana E. Oligoclonal bands in multiple sclerosis patients: worse prognosis. Neurol Res 2012;34(9):889-892.
22. Schneger R, Souza MD, Schindler C, Grize L, Dellas S, Radne EW. Prediction of long-term disability in multiple sclerosis. Mult Scler 2012;18(1):31-38.
23. Swanton JK, Rovira A, Tintore M, Altmann DR, Barkhof F, Filippi M et al. MRI criteria for multiple sclerosis in patient presenting with clinically isolated syndromes:a multicentre retrospective study. Lancet Neurol 2007;6:677-686.
24. Autor, 2011.
25. Aktas O, Wattjes MP, Sangel M, Hartung HP. Diagnosis of multiple sclerosis: revision of the McDonald criteria 2017. Nervenarzt. 2018 Jun 6. doi: 10.1007/s00115-018-0550-0.
26. Drulovic J, Basic-Kes V, Grgic S, Vojinovic S, Dincic E, Toncev G et al. The Prevalence of Pain in Adults with Multiple Sclerosis: A Multicenter Cross-Sectional Survey. Pain Med. 2015; 16(8): 1597-602.
27. Mesaroš Š, Drulović J. Dijagnoza muliple skleroze: uloga magnetne rezonance. U: Drulović J. Multipla skleroza. Medicinski fakultet Univerziteta u Beogradu 2013; 119-142.
28. Caucheteux N, Maarouf A, Genevray M, Leray E, Deschamps R, Chaunu MP et al. Criteria improving multiple sclerosis diagnosis at the first MRI. J Neurol. 2015; 262(4):979-87.
29. Hyun JW, Huh Sy, Kim W et al. Evaluation of 2016 MAGNIMS MRI criteria for dissemination in space in patients with a clinically isolated syndrome. Mult Scler. 2018; 24(6): 758-766.
30. Lourenco P, Shiran A, Saeedi J, Oger J, Schreiber A, Tremlett H. Oligoclonal bands and cerebrospinal fluid markers in multiple sclerosis: associations with disease course and progression. Mult Scler 2012;1(0):1-8.
31. Filippi M, Rocca MA, Ciccarelli O, De Stefano N, Evangelou N, Kappos L et al. MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus guidelines. Lancet Neurol. 2016; 15(3): 292-303.
32. Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G et al. Diagnosis of multiple sclerosis: 2017 revision of the McDonald criteria. Lancet Neurol. 2018; 17(2):162-173.
33. Gaetani L, Prosperini L, Mancini A et al. 2017 revisions of McDonald criteria shorten the time to diagnosis of multiple sclerosis in clinically isolated syndromes. J Neurol. 2018;265(11):2684-2687.
34. Ruet A, Arrambide G, Brochet B, Auger C, Simon E, Rovira A, et al. Early predictors of multiple sclerosis after a typical clinically isolated syndrome. Mult Scler 2014; 20: 1721–26.
35. Castello MS, Alcala C, Mathur D, Rodas GL, Marti MB, Casanova B. Immunodetection of oligoclonal bands in serum and CSF of Multiple Sclerosis patients. Ann Neurosci. 2015; 22(1): 54.
36. Granď Maison F, Yeung M, Morrow SA, Lee L, Emond F, Ward BJ, et al. Sequencing of disease-modifying therapies for relapsing-remitting multiple sclerosis: a theoretical approach to optimizing treatment. Curr Med Res Opin. 2018; 34(8):1419-1430.
37. Mero IL, Gustavsen MW, Saether HS, Flam ST, Hansen PB, Sondergaard HB et al. Oligoclonal band status in Scandinavian multiple sclerosis patients is associated with specific genetic risk alleles. PLos One. 2013;8(3):e58352 doi:10.1371/journal.pone.0058352
38. Imrell K, Landtblom AM, Hillert J, Masterman T. Multiple sclerosis with and without CSF bands: Clinically indistinguishable but immunogenetically distinct. Neurol. 2006;67(6): 1062-4.
39. Drulović J. Terapija koja modifikuje prirodni tok multiple skleroze. U: Drulović J. Multipla skleroza. Medicinski fakultet Univerziteta u Beogradu 2013; 161-182.
40. Drulovic J, Cukic M, Grgic S, Dincic E, Raicevic R, Congor N et al. The Impact of Betaplus Program on patient treatment satisfaction with interferon beta-1b in multiple sclerosis: Multicenter cross-sectional survey in the Western Balkan countries. Mult Scler Relat Disord. 2016; 11: 56-61.
41. Yadav SK, Mindur JE, Ito K, Dhib-Jalbut S. Advances in the immunopathogenesis of multiple sclerosis. Curr Opin Neurol. 2015;28:206–19.
42. Ontaneda D, Fox RJ. Progressive multiple sclerosis. Curr Opin Neurol. 2015;28:237–43.
43. Lanza CV, Bramanti P, Mazzon E et al. Biomarkers identification for PML monitoring, during Natalizumab (Tysabri®) treatment in Relapsing-Remitting Multiple Sclerosis. Mult Scler Relat Disord. 2018;20:93-99.
44. Autor, 2014.
45. Engelborghs S et al. Consensus guidelines for lumbar puncture in patients with neurological diseases. Alzheimers Dement (Amst). 2017; 8: 111–126.
46. Dominques RB et all. The cerebrospinal fluid in multiple sclerosis: far beyond the bands. Einstein. 2017.;15(1):100-104.
47. Brändle SM, Obermeier B, Senel M. et al. Distinct oligoclonal band antibodies in multiple sclerosis recognize ubiquitous self-proteins.PNAS. 2016; 113(28) 7864-7869
48. Mc Nicholas N, Hutchinson M, McGuigan C, Chataway J. 2017 McDonald diagnostic criteria: A review of the evidence. Mult Scler Rel Disord. 2018; 24:48-54.
49. Arrambide G et al. The value of oligoclonal bands in the multiple sclerosis diagnostic criteria. Brain. 2018; 141(4): 1-10.
50. Frau J, Villar LM, Sardu C, Secci MA, Schirru L, Ferraro D et al. Intrathecal oligoclonal bands synthesis in multiple sclerosis: is it always a prognostic factor? J Neurol. 2018; 265(2):424-430.
51. Sun X, Bakhti M, Fitzner D et al. Quantified CSF antibody reactivity against myelin in multiple sclerosis. Ann Clin Transl Neurol. 2015; 2(12):1116–1123.
52. Katsavos S, Anagnostouli M. Biomarkers in Multiple Sclerosis: An Up-to-Date Overview. Mult Scler Int. 2013; 2013: 340-508.
53. Kuhle J, Disanto G, Dobson R, Adiutori R, Bianchi I, Topping J et al. Conversion from clinically isolated syndrome to multiple sclerosis: A large multicenter study. MSJ 2015; 21(8):1 013–24.
54. Huang WJ, Chen WW, Zhang X. Multiple sclerosis: Pathology, diagnosis and treatments. Exp Ther Med. 2017; 13(6): 3163–3166.
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2020/09/30
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