Clinical use of antibodies in multiple sclerosis

Czech version

Authors: A. Bartoš
Authors‘ workplace: Neurologická klinika 3. LF UK a FNKV, Praha
Published in: Cesk Slov Neurol N 2008; 71/104(1): 26-33
Category: Review Article

Overview

There is much evidence to implicate B cells and antibody immunity in the pathogenesis of multiple sclerosis (MS) in the last decade. The presence of cerebrospinal fluid oligoclonal bands of IgG class not detectable in serum provides powerful evidence for the diagnosis of MS, since it occurs in 95 % of patients with MS. The determination of antibody specificity has been unsuccessful so far. The search for an antibody or a combination of antibodies continues in order to improve the diagnosis, the classification and the prediction of the further course. Antimyelin antibodies to myelin oligodendrocyte glycoprotein and myelin basic protein are the most popular in the recent years. Their prognostic value originally accepted with a great expectation is not confirmed with the latest data. Evidence of axonal pathology was reflected in the interest in antiaxonal antibodies. The results are not consistent, however. New methods and analysis of other factors of humoral immunity may result in identifying antibodies as biological markers of MS.

Key words:
multiple sclerosis, cerebrospinal fluid, antibody, intrathecal synthesis, oligoclonal bands, immunoglobulins

Sources

1. Archelos JJ, Storch MK, Hartung HP. The role of B cells and autoantibodies in multiple sclerosis. Ann Neurol 2000; 47: 694-706.

2. Cross AH, Trotter JL, Lyons J. B cells and antibodies in CNS demyelinating disease. J Neuroimmunol 2001; 112: 1-14.

3. Cross AH, Stark JL. Humoral immunity in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis. Immunol Res 2005; 32: 85-98.

4. Teunissen CE, Dijkstra C, Polman C. Biological markers in CSF and blood for axonal degeneration in multiple sclerosis. Lancet Neurol 2005; 4: 32-41.

5. Martino G, Adorini L, Rieckmann P, Hillert J, Kallmann B, Comi G et al. Inflammation in multiple sclerosis: the good, the bad, and the complex. Lancet Neurol 2002; 1: 499-509.

6. Lucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 2000; 47: 707-717.

7. Sorensen PS. Treatment of multiple sclerosis with intravenous immunoglobulin: review of clinical trials. Neurol Sci 2003; 24 Suppl 4: S227-230.

8. Keegan M, Konig F, McClelland R, Bruck W, Morales Y, Bitsch A et al. Relation between humoral pathological changes in multiple sclerosis and response to therapeutic plasma exchange. Lancet 2005; 366: 579-582.

9. Cross AH, Stark JL, Lauber J, Ramsbottom MJ, Lyons JA. Rituximab reduces B cells and T cells in cerebrospinal fluid of multiple sclerosis patients. J Neuroimmunol 2006; 180: 63-70.

10. Reiber H, Lange P. Quantification of virus-specific antibodies in cerebrospinal fluid and serum: sensitive and specific detection of antibody synthesis in brain. Clin Chem 1991; 37: 1153-1160.

11. Štourač P, Bednářová J. Intratekální, antivirová a oligoklonální IgG syntéza u sclerosis multiplex a její význam v diferenciální diagnostice neurologických onemocnění. Klin Biochem Metabol 2000; 8 (4): 204-208.

12. Bednarova J, Stourac P, Adam P. Relevance of immunological variables in neuroborreliosis and multiple sclerosis. Acta Neurol Scand 2005; 112: 97-102.

13. Derfuss T, Hohlfeld R, Meinl E. Intrathecal antibody (IgG) production against human herpesvirus type 6 occurs in about 20% of multiple sclerosis patients and might be linked to a polyspecific B-cell response. J Neurol 2005; 252: 968-971.

14. Hughes LE, Bonell S, Natt RS, Wilson C, Tiwana H, Ebringer A et al. Antibody responses to Acinetobacter spp. and Pseudomonas aeruginosa in multiple sclerosis: prospects for diagnosis using the myelin-acinetobacter-neurofilament antibody index. Clin Diagn Lab Immunol 2001; 8: 1181-1188.

15. Ebringer A, Hughes L, Rashid T, Wilson C. Acinetobacter immune responses in multiple sclerosis: etiopathogenetic role and its possible use as a diagnostic marker. Arch Neurol 2005; 62: 33-36.

16. Annunziata P, Giorgio A, De Santi L, Zipoli V, Portaccio E, Amato MP et al. Absence of cerebrospinal fluid oligoclonal bands is associated with delayed disability progression in relapsing-remitting MS patients treated with interferon-beta. J Neurol Sci 2006; 244: 97-102.

17. Reindl M, Khalil M, Berger T. Antibodies as biological markers for pathophysiological processes in MS. J Neuroimmunol 2006; 180: 50-62.

18. Acarin N, Rio J, Fernandez AL, Tintore M, Duran I, Galan I et al. Different antiganglioside antibody pattern between relapsing-remitting and progressive multiple sclerosis. Acta Neurol Scand 1996; 93: 99-103.

19. Genain CP, Cannella B, Hauser SL, Raine CS. Identification of autoantibodies associated with myelin damage in multiple sclerosis. Nat Med 1999; 5: 170-175.

20. Berger T, Rubner P, Schautzer F, Egg R, Ulmer H, Mayringer I et al. Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event. N Engl J Med 2003; 349: 139-145.

21. Reindl M, Khantane S, Ehling R, Schanda K, Lutterotti A, Brinkhoff C et al. Serum and cerebrospinal fluid antibodies to Nogo-A in patients with multiple sclerosis and acute neurological disorders. J Neuroimmunol 2003; 145: 139-147.

22. Markovic M, Trajkovic V, Drulovic J, Mesaros S, Stojsavljevic N, Dujmovic I et al. Antibodies against myelin oligodendrocyte glycoprotein in the cerebrospinal fluid of multiple sclerosis patients. J Neurol Sci 2003; 211: 67-73.

23. Lily O, Palace J, Vincent A. Serum autoantibodies to cell surface determinants in multiple sclerosis: a flow cytometric study. Brain 2004; 127: 269-279.

24. Menge T, Lalive PH, von Budingen HC, Cree B, Hauser SL, Genain CP. Antibody responses against galactocerebroside are potential stage-specific biomarkers in multiple sclerosis. J Allergy Clin Immunol 2005; 116: 453-459.

25. Onoue H, Satoh JI, Ogawa M, Tabunoki H, Yamamura T. Detection of anti-Nogo receptor autoantibody in the serum of multiple sclerosis and controls. Acta Neurol Scand 2007; 115: 153-160.

26. Silber E, Semra YK, Gregson NA, Sharief MK. Patients with progressive multiple sclerosis have elevated antibodies to neurofilament subunit. Neurology 2002; 58: 1372-1381.

27. Eikelenboom MJ, Petzold A, Lazeron RH, Silber E, Sharief M, Thompson EJ et al. Multiple sclerosis: Neurofilament light chain antibodies are correlated to cerebral atrophy. Neurology 2003; 60: 219-223.

28. Ehling R, Lutterotti A, Wanschitz J, Khalil M, Gneiss C, Deisenhammer F et al. Increased frequencies of serum antibodies to neurofilament light in patients with primary chronic progressive multiple sclerosis. Mult Scler 2004; 10: 601-606.

29. Bartoš A, Fialová L, Soukupová J, Kukal J, Malbohan I, Piťha J. Antibodies against light neurofilaments in multiple sclerosis patients. Acta Neurol Scand 2007, in press.

30. Bartoš A, Fialová L, Soukupová J, Kukal J, Malbohan I, Piťha J. Elevated intrathecal antibodies against the medium neurofilament subunit in multiple sclerosis. J Neurol 2007; 254: 20-25.

31. Heinzlef O, Weill B, Johanet C, Sazdovitch V, Caillat-Zucman S, Tournier-Lasserve E et al. Anticardiolipin antibodies in patients with multiple sclerosis do not represent a subgroup of patients according to clinical, familial, and biological characteristics. J Neurol Neurosurg Psychiatry 2002; 72: 647-649.

32. Mayo I, Arribas J, Villoslada P, Alvarez DoForno R, Rodriguez-Vilarino S, Montalban X et al. The proteasome is a major autoantigen in multiple sclerosis. Brain 2002; 125: 2658-2667.

33. Almeras L, Lefranc D, Drobecq H, de Seze J, Dubucquoi S, Vermersch P et al. New antigenic candidates in multiple sclerosis: identification by serological proteome analysis. Proteomics 2004; 4: 2184-2194.

34. Bitsch A, Dressel A, Meier K, Bogumil T, Deisenhammer F, Tumani H et al. Autoantibody synthesis in primary progressive multiple sclerosis patients treated with interferon beta-1b. J Neurol 2004; 251: 1498-1501.

35. Chiba S, Yokota S, Yonekura K, Tanaka S, Furuyama H, Kubota H et al. Autoantibodies against HSP70 family proteins were detected in the cerebrospinal fluid from patients with multiple sclerosis. J Neurol Sci 2006; 241: 39-43.

36. Cid C, Regidor I, Alcazar A. Anti-heat shock protein 90beta antibodies are detected in patients with multiple sclerosis during remission. J Neuroimmunol 2007; 184: 223-226.

37. Qin Y, Duquette P. B-cell immunity in MS. Int MS J 2003; 10: 110-120.

38. Correale J, de los Milagros Bassani Molinas M. Oligoclonal bands and antibody responses in multiple sclerosis. J Neurol 2002; 249: 375-389.

39. Havrdová E. Neuroimunologie. Praha: Maxdorf Jessenius 2001.

40. Wekerle H, Hohlfeld R. Molecular mimicry in multiple sclerosis. N Engl J Med 2003; 349: 185-186.

41. Hughes LE, Smith PA, Bonell S, Natt RS, Wilson C, Rashid T et al. Cross-reactivity between related sequences found in Acinetobacter sp., Pseudomonas aeruginosa, myelin basic protein and myelin oligodendrocyte glycoprotein in multiple sclerosis. J Neuroimmunol 2003; 144: 105-115.

42. Prat A, Antel J. Pathogenesis of multiple sclerosis. Curr Opin Neurol 2005; 18: 225-230.

43. Andersson M, Alvarez-Cermeno J, Bernardi G, Cogato I, Fredman P, Frederiksen J et al. Cerebrospinal fluid in the diagnosis of multiple sclerosis: a consensus report. J Neurol Neurosurg Psychiatry 1994; 57: 897-902.

44. Freedman MS, Thompson EJ, Deisenhammer F, Giovannoni G, Grimsley G, Keir G et al. Recommended standard of cerebrospinal fluid analysis in the diagnosis of multiple sclerosis: a consensus statement. Arch Neurol 2005; 62: 865-870.

45. Deisenhammer F, Bartos A, Egg R, Gilhus NE, Giovannoni G, Rauer S et al. Guidelines on routine cerebrospinal fluid analysis. Report from an EFNS task force. Eur J Neurol 2006; 13: 913-922.

46. Link H, Huang YM. Oligoclonal bands in multiple sclerosis cerebrospinal fluid: an update on methodology and clinical usefulness. J Neuroimmunol 2006; 180: 17-28.

47. Villar LM, Masjuan J, Sadaba MC, Gonzalez-Porque P, Plaza J, Bootello A et al. Early differential diagnosis of multiple sclerosis using a new oligoclonal band test. Arch Neurol 2005; 62: 574-577.

48. Reiber H, Peter JB. Cerebrospinal fluid analysis: disease-related data patterns and evaluation programs. J Neurol Sci 2001; 184: 101-122.

49. Reiber H, Ungefehr S, Jacobi C. The intrathecal, polyspecific and oligoclonal immune response in multiple sclerosis. Mult Scler 1998; 4: 111-117.

50. Sellebjerg F, Christiansen M, Rasmussen LS, Jaliachvili I, Nielsen PM, Frederiksen JL. The cerebrospinal fluid in multiple sclerosis. Quantitative assessment of intrathecal IgG synthesis by empirical formulae. Eur J Neurol 1996; 3: 548-559.

51. Izquierdo G, Angulo S, Garcia-Moreno JM, Gamero MA, Navarro G, Gata JM et al. Intrathecal IgG synthesis: marker of progression in multiple sclerosis patients. Acta Neurol Scand 2002; 105: 158-163.

52. Villar LM, Masjuan J, Gonzalez-Porque P, Plaza J, Sadaba MC, Roldan E et al. Intrathecal IgM synthesis is a prognostic factor in multiple sclerosis. Ann Neurol 2003; 53: 222-226.

53. Perini P, Ranzato F, Calabrese M, Battistin L, Gallo P. Intrathecal IgM production at clinical onset correlates with a more severe disease course in multiple sclerosis. J Neurol Neurosurg Psychiatry 2006; 77: 953-955.

54. Sastre-Garriga J, Tintore M, Rovira A, Grive E, Pericot I, Comabella M et al. Conversion to multiple sclerosis after a clinically isolated syndrome of the brainstem: cranial magnetic resonance imaging, cerebrospinal fluid and neurophysiological findings. Mult Scler 2003; 9: 39-43

55. Masjuan J, Alvarez-Cermeno JC, Garcia-Barragan N, Diaz-Sanchez M, Espino M, Sadaba MC et al. Clinically isolated syndromes: a new oligoclonal band test accurately predicts conversion to MS. Neurology 2006; 66: 576-578.

56. Schwarz M, Spector L, Gortler M, Weisshaus O, Glass-Marmor L, Karni A et al. Serum anti-Glc(alpha1,4)Glc(alpha) antibodies as a biomarker for relapsing-remitting multiple sclerosis. J Neurol Sci 2006; 244: 59-68.

57. Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 2005; 202: 473-477.

58. Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 2004; 364: 2106-2112.

59. Krejsek J, Kopecký O, Taláb R. Imunopatogeneze roztroušené sklerózy. Neurol pro Praxi 2002; 3 (5): 236-243.

60. Vincent A, Lily O, Palace J. Pathogenic autoantibodies to neuronal proteins in neurological disorders. J Neuroimmunol 1999; 100: 169-180.

61. Reindl M, Linington C, Brehm U, Egg R, Dilitz E, Deisenhammer F et al. Antibodies against the myelin oligodendrocyte glycoprotein and the myelin basic protein in multiple sclerosis and other neurological diseases: a comparative study. Brain 1999; 122 (Pt 11): 2047-2056.

62. O'Connor KC, Chitnis T, Griffin DE, Piyasirisilp S, Bar-Or A, Khoury S et al. Myelin basic protein-reactive autoantibodies in the serum and cerebrospinal fluid of multiple sclerosis patients are characterized by low-affinity interactions. J Neuroimmunol 2003; 136: 140-148.

63. Sellebjerg F, Jensen CV, Christiansen M. Intrathecal IgG synthesis and autoantibody-secreting cells in multiple sclerosis. J Neuroimmunol 2000; 108: 207-215.

64. Khalil M, Reindl M, Lutterotti A, Kuenz B, Ehling R, Gneiss C et al. Epitope specificity of serum antibodies directed against the extracellular domain of myelin oligodendrocyte glycoprotein: Influence of relapses and immunomodulatory treatments. J Neuroimmunol 2006; 174: 147-156.

65. Rauer S, Euler B, Reindl M, Berger T. Antimyelin antibodies and the risk of relapse in patients with a primary demyelinating event. J Neurol Neurosurg Psychiatry 2006; 77: 739-742.

66. Gaertner S, de Graaf KL, Greve B, Weissert R. Antibodies against glycosylated native MOG are elevated in patients with multiple sclerosis. Neurology 2004; 63: 2381-2383.

67. Zhou D, Srivastava R, Nessler S, Grummel V, Sommer N, Bruck W et al. Identification of a pathogenic antibody response to native myelin oligodendrocyte glycoprotein in multiple sclerosis. Proc Natl Acad Sci U S A 2006; 103: 19057-19062.

68. Lampasona V, Franciotta D, Furlan R, Zanaboni S, Fazio R, Bonifacio E et al. Similar low frequency of anti-MOG IgG and IgM in MS patients and healthy subjects. Neurology 2004; 62: 2092-2094.

69. Mantegazza R, Cristaldini P, Bernasconi P, Baggi F, Pedotti R, Piccini I et al. Anti-MOG autoantibodies in Italian multiple sclerosis patients: specificity, sensitivity and clinical association. Int Immunol 2004; 16: 559-565.

70. Zadro I, Brinar VV, Horvat G, Brinar M. Clinical relevance of antibodies against myelin oligodendrocyte glycoprotein in different clinical types of multiple sclerosis. Clin Neurol Neurosurg 2007; 109: 23-26.

71. Lalive PH, Menge T, Delarasse C, Della Gaspera B, Pham-Dinh D, Villoslada P et al. Antibodies to native myelin oligodendrocyte glycoprotein are serologic markers of early inflammation in multiple sclerosis. Proc Natl Acad Sci USA 2006; 103: 2280-2285.

72. Kuhle J, Pohl C, Mehling M, Edan G, Freedman MS, Hartung HP et al. Lack of association between antimyelin antibodies and progression to multiple sclerosis. N Engl J Med 2007; 356: 371-378.

73. Lim ET, Berger T, Reindl M, Dalton CM, Fernando K, Keir G et al. Anti-myelin antibodies do not allow earlier diagnosis of multiple sclerosis. Mult Scler 2005; 11: 492-494.

74. Pelayo R, Tintore M, Montalban X, Rovira A, Espejo C, Reindl M et al. Antimyelin antibodies with no progression to multiple sclerosis. N Engl J Med 2007; 356: 426-428.

75. Pittock SJ, Reindl M, Achenbach S, Berger T, Bruck W, Konig F et al. Myelin oligodendrocyte glycoprotein antibodies in pathologically proven multiple sclerosis: frequency, stability and clinicopathologic correlations. Mult Scler 2007; 13: 7-16.

76. Bjartmar C, Wujek JR, Trapp BD. Axonal loss in the pathology of MS: consequences for understanding the progressive phase of the disease. J Neurol Sci 2003; 206: 165-171.

77. Bartoš A, Piťha J. Axonální patologie v časných stadiích roztroušené sklerózy. Cesk Slov Neurol N 2004; 67/100 (5): 381.

78. Piťha J, Havrdová E. Axonální patologie u roztroušené sklerózy. Cesk Slov Neurol N 2005; 68/101 (3): 154–158.

79. Štourač P. Paraneoplastické autoimunitní neurologické syndromy. Cesk Slov Neurol N 2005; 68/101 (2): 80-89.

80. Bartos A, Stourac P, Rusina R, Sejdova M, Velenska Z. Paraneoplastische Degeneration des Kleinhirns bei einem Ovarialkarzinom: anti-Yo positive Immunreaktivität der Kleinhirn- und Tumorzellen. Nervenarzt 2002; 73: 995-998.