Sera of glaucoma patients show autoantibodies against myelin basic protein and complex autoantibody profiles against human optic nerve antigens

  • Stephanie C. Joachim
  • Jan Reichelt
  • Simone Berneiser
  • Norbert Pfeiffer
  • Franz H. GrusEmail author



The aim of this study was to gain more information about the possible immunological mechanisms in glaucoma. We analyzed the complex autoantibody patterns against human optic nerve antigens in sera of patients with glaucoma and tried to identify important antigens.


Sera of 133 patients were included: healthy control subjects (n = 44), primary open-angle glaucoma (n = 44), and normal tension glaucoma patients (n = 45). The sera were tested against Western blots of human optic nerve, and antibody bands were visualized with chloronaphthol. IgG antibody patterns were analyzed by multivariate statistical techniques, and the most significant antigens were identified by mass spectrometry (Maldi-TOFTOF).


All subjects, even healthy ones, showed different and complex antibody patterns. Glaucoma groups showed specific up- and down-regulations of antibody reactivities compared to the control group. The multivariate analysis of discriminance found significant differences (P < 0.05) in IgG antibody profiles against human optic nerve antigens between both glaucoma groups and healthy subjects. The identified antigens include: myelin basic protein (up-regulated in the POAG group), glial fibrillary acidic protein (down-regulated in the glaucoma groups), and vimentin (down-regulated in the glaucoma groups in comparison to controls).


Using human optic nerve antigen, we were able to demonstrate that complex IgG autoantibody patterns exist in sera of patients with glaucoma. Large correlations between the given and our previous studies using bovine optic nerve antigens could be seen. Furthermore, anti-myelin basic protein antibodies, which can also be detected in patients with multiple sclerosis, were found in sera of glaucoma patients.


Antibody profile Glaucoma Myelin basic protein Optic nerve 



This study was supported in part by the DFG grant Gr1463/4–1 (Deutsche Forschungsgemeinschaft) and the Else Kröner Fresenius Foundation.


  1. 1.
    Quigley HA (1996) Number of people with glaucoma worldwide. Br J Ophthalmol 80(5):389–393PubMedCrossRefGoogle Scholar
  2. 2.
    Quigley HA, Broman AT (2006) The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol 90(3):262–267PubMedCrossRefGoogle Scholar
  3. 3.
    Garcia-Valenzuela E, Shareef S, Walsh J, Sharma SC (1995) Programmed cell death of retinal ganglion cells during experimental glaucoma. Exp Eye Res 61(1):33–44PubMedCrossRefGoogle Scholar
  4. 4.
    Flammer J, Orgul S, Costa VP et al (2002) The impact of ocular blood flow in glaucoma. Prog Retin Eye Res 21(4):359–393PubMedCrossRefGoogle Scholar
  5. 5.
    Osborne NN, Melena J, Chidlow G, Wood JP (2001) A hypothesis to explain ganglion cell death caused by vascular insults at the optic nerve head: possible implication for the treatment of glaucoma. Br J Ophthalmol 85(10):1252–1259PubMedCrossRefGoogle Scholar
  6. 6.
    Kitazawa Y (2001) Open-angle glaucoma clinical presentation and management. Nippon Ganka Gakkai Zasshi 105(12):828–842PubMedGoogle Scholar
  7. 7.
    Tezel G, Hernandez R, Wax MB (2000) Immunostaining of heat shock proteins in the retina and optic nerve head of normal and glaucomatous eyes. Arch Ophthalmol 118(4):511–518PubMedGoogle Scholar
  8. 8.
    Tezel G, Seigel GM, Wax MB (1998) Autoantibodies to small heat shock proteins in glaucoma. Invest Ophthalmol Vis Sci 39(12):2277–2287PubMedGoogle Scholar
  9. 9.
    Wax MB, Tezel G, Kawase K, Kitazawa Y (2001) Serum autoantibodies to heat shock proteins in glaucoma patients from Japan and the United States. Ophthalmology 108(2):296–302PubMedCrossRefGoogle Scholar
  10. 10.
    Maruyama I, Ikeda Y, Nakazawa M, Ohguro H (2002) Clinical roles of serum autoantibody against neuron-specific enolase in glaucoma patients. Tohoku J Exp Med 197(3):125–132PubMedCrossRefGoogle Scholar
  11. 11.
    Grus FH, Joachim SC, Bruns K et al (2006) Serum autoantibodies to {alpha}-fodrin are present in glaucoma patients from Germany and the United States. Invest Ophthalmol Vis Sci 47(3):968–976PubMedCrossRefGoogle Scholar
  12. 12.
    Yang J, Tezel G, Patil RV et al (2001) Serum autoantibody against glutathione S-transferase in patients with glaucoma. Invest Ophthalmol Vis Sci 42(6):1273–1276PubMedGoogle Scholar
  13. 13.
    Tezel G, Edward DP, Wax MB (1999) Serum autoantibodies to optic nerve head glycosaminoglycans in patients with glaucoma. Arch Ophthalmol 117(7):917–924PubMedGoogle Scholar
  14. 14.
    Society TEG (2006) Terminology and guidelines for glaucoma. IInd edition
  15. 15.
    Reichelt J, Joachim SC, Pfeiffer N, Grus FH (2007) Analysis of autoantibodies against human retinal antigens in sera of patients with glaucoma and ocular hypertension. accepted in Curr Eye ResGoogle Scholar
  16. 16.
    Grus FH, Augustin AJ, Zimmermann CW (1997) Computer-supported analysis (MegaBlot) of allopurinol-induced changes in the autoantibody repertoires of rats suffering from experimental lens-induced uveitis. Electrophoresis 18(3–4):516–519PubMedCrossRefGoogle Scholar
  17. 17.
    Singer HS, Loiselle CR, Lee O et al (2003) Anti-basal ganglia antibody abnormalities in Sydenham chorea. J Neuroimmunol 136(1–2):154–161PubMedCrossRefGoogle Scholar
  18. 18.
    Wendlandt JT, Grus FH, Hansen BH, Singer HS (2001) Striatal antibodies in children with Tourette’s syndrome: multivariate discriminant analysis of IgG repertoires. J Neuroimmunol 119(1):106–113PubMedCrossRefGoogle Scholar
  19. 19.
    Zimmermann CW, Grus FH, Dux R (1995) Multivariate statistical comparison of autoantibody-repertoires (western blots) by discriminant analysis. Electrophoresis 16(6):941–947PubMedCrossRefGoogle Scholar
  20. 20.
    Joachim SC, Pfeiffer N, Grus FH (2005) Autoantibodies in patients with glaucoma: a comparison of IgG serum antibodies against retinal, optic nerve, and optic nerve head antigens. Graefes Arch Clin Exp Ophthalmol 243(8):817–823PubMedCrossRefGoogle Scholar
  21. 21.
    Grus FH, Joachim SC, Hoffmann EM, Pfeiffer N (2004) Complex autoantibody repertoires in patients with glaucoma. Mol Vis 10:132–137PubMedGoogle Scholar
  22. 22.
    Romano C, Barrett DA, Li Z et al (1995) Anti-rhodopsin antibodies in sera from patients with normal-pressure glaucoma. Invest Ophthalmol Vis Sci 36(10):1968–1975PubMedGoogle Scholar
  23. 23.
    Wax MB, Tezel G, Saito I et al (1998) Anti-Ro/SS-A positivity and heat shock protein antibodies in patients with normal-pressure glaucoma. Am J Ophthalmol 125(2):145–157PubMedCrossRefGoogle Scholar
  24. 24.
    Joachim SC, Grus FH, Pfeiffer N (2003) Analysis of autoantibody repertoires in sera of patients with glaucoma. Eur J Ophthalmol 13(9–10):752–758PubMedGoogle Scholar
  25. 25.
    Vojdani A, Vojdani E, Cooper E (2003) Antibodies to myelin basic protein, myelin oligodendrocytes peptides, alpha-beta-crystallin, lymphocyte activation and cytokine production in patients with multiple sclerosis. J Intern Med 254(4):363–374PubMedCrossRefGoogle Scholar
  26. 26.
    Chamczuk AJ, Ursell M, O’Connor P et al (2002) A rapid ELISA-based serum assay for myelin basic protein in multiple sclerosis. J Immunol Methods 262(1–2):21–27PubMedCrossRefGoogle Scholar
  27. 27.
    Reindl M, Linington C, Brehm U et al (1999) Antibodies against the myelin oligodendrocyte glycoprotein and the myelin basic protein in multiple sclerosis and other neurological diseases: a comparative study. Brain 122 (Pt 11):2047–2056PubMedCrossRefGoogle Scholar
  28. 28.
    Schmidt S, Haase CG, Bezman L et al (2001) Serum autoantibody responses to myelin oligodendrocyte glycoprotein and myelin basic protein in X-linked adrenoleukodystrophy and multiple sclerosis. J Neuroimmunol 119(1):88–94PubMedCrossRefGoogle Scholar
  29. 29.
    Paterson PY, Day ED, Whitacre CC et al (1981) Endogenous myelin basic protein-serum factors (MBP-SFs) and anti-MBP antibodies in humans. Occurrence in sera of clinically well subjects and patients with multiple sclerosis. J Neurol Sci 52(1):37–51PubMedCrossRefGoogle Scholar
  30. 30.
    Warren KG, Catz I (1994) Relative frequency of autoantibodies to myelin basic protein and proteolipid protein in optic neuritis and multiple sclerosis cerebrospinal fluid. J Neurol Sci 121(1):66–73PubMedCrossRefGoogle Scholar
  31. 31.
    Guo L, Li Y, Lin H et al (2004) Evaluation of a rat model of experimental autoimmune encephalomyelitis with human MBP as antigen. Cell Mol Immunol 1(5):387–391PubMedGoogle Scholar
  32. 32.
    Schluesener HJ, Sobel RA, Linington C, Weiner HL (1987) A monoclonal antibody against a myelin oligodendrocyte glycoprotein induces relapses and demyelination in central nervous system autoimmune disease. J Immunol 139(12):4016–4021PubMedGoogle Scholar
  33. 33.
    Berger T, Rubner P, Schautzer F et al (2003) Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event. N Engl J Med 349(2):139–145PubMedCrossRefGoogle Scholar
  34. 34.
    Tomassini V, De Giglio L, Reindl M et al (2007) Anti-myelin antibodies predict the clinical outcome after a first episode suggestive of MS. Mult Scler 13(9):1086-1094PubMedCrossRefGoogle Scholar
  35. 35.
    O’Riordan JI, Thompson AJ, Kingsley DP et al (1998) The prognostic value of brain MRI in clinically isolated syndromes of the CNS. A 10-year follow-up. Brain 121 (Pt 3):495–503PubMedCrossRefGoogle Scholar
  36. 36.
    Lim ET, Berger T, Reindl M et al (2005) Anti-myelin antibodies do not allow earlier diagnosis of multiple sclerosis. Mult Scler 11(4):492–494PubMedCrossRefGoogle Scholar
  37. 37.
    Norgren N, Sundstrom P, Svenningsson A et al (2004) Neurofilament and glial fibrillary acidic protein in multiple sclerosis. Neurology 63(9):1586–1590PubMedGoogle Scholar
  38. 38.
    Sanna G, Piga M, Terryberry JW et al (2000) Central nervous system involvement in systemic lupus erythematosus: cerebral imaging and serological profile in patients with and without overt neuropsychiatric manifestations. Lupus 9(8):573–583PubMedCrossRefGoogle Scholar
  39. 39.
    Chen H, Weber AJ (2002) Expression of glial fibrillary acidic protein and glutamine synthetase by Muller cells after optic nerve damage and intravitreal application of brain-derived neurotrophic factor. Glia 38(2):115–125PubMedCrossRefGoogle Scholar
  40. 40.
    Lam TT, Kwong JM, Tso MO (2003) Early glial responses after acute elevated intraocular pressure in rats. Invest Ophthalmol Vis Sci 44(2):638–645PubMedCrossRefGoogle Scholar
  41. 41.
    Singh VK, Warren R, Averett R, Ghaziuddin M (1997) Circulating autoantibodies to neuronal and glial filament proteins in autism. Pediatr Neurol 17(1):88–90PubMedCrossRefGoogle Scholar
  42. 42.
    Stuart BM, Gregson NA (1998) Cerebral calcification in a patient with systemic lupus erythematosus and a monoclonal IgG reactive with glial fibrillary acidic protein. Br J Rheumatol 37(12):1355–1357PubMedCrossRefGoogle Scholar
  43. 43.
    Shibuya M, Matsuki N, Fujiwara K et al (2007) Autoantibodies against glial fibrillary acidic protein (GFAP) in cerebrospinal fluids from Pug dogs with necrotizing meningoencephalitis. J Vet Med Sci 69(3):241–245PubMedCrossRefGoogle Scholar
  44. 44.
    Lewis GP, Erickson PA, Guerin CJ et al (1989) Changes in the expression of specific Muller cell proteins during long-term retinal detachment. Exp Eye Res 49(1):93–111PubMedCrossRefGoogle Scholar
  45. 45.
    Brown C, Pedersen J, Underwood JR et al (1986) Autoantibodies to intermediate filaments in acute viral hepatitis A, B and non-A, non-B are directed against vimentin. J Clin Lab Immunol 19(1):1–4PubMedGoogle Scholar
  46. 46.
    Yang Y, Fujita J, Bandoh S et al (2002) Detection of antivimentin antibody in sera of patients with idiopathic pulmonary fibrosis and non-specific interstitial pneumonia. Clin Exp Immunol 128(1):169–174PubMedCrossRefGoogle Scholar
  47. 47.
    Poletaev A, Osipenko L (2003) General network of natural autoantibodies as immunological homunculus (Immunculus). Autoimmun Rev 2(5):264–271PubMedCrossRefGoogle Scholar
  48. 48.
    Kulberg AY (1999) Immunoglobulins and Antibodies. Russ J Immunol 4(3):241–242PubMedGoogle Scholar
  49. 49.
    Erlanger BF (1989) Some thoughts on the structural basis of internal imagery. Immunol Today 10(5):151–152PubMedCrossRefGoogle Scholar
  50. 50.
    Scofield RH (2004) Autoantibodies as predictors of disease. Lancet 363(9420):1544–1546PubMedCrossRefGoogle Scholar
  51. 51.
    Shmerling RH (2003) Autoantibodies in systemic lupus erythematosus-there before you know it. N Engl J Med 349(16):1499–1500PubMedCrossRefGoogle Scholar
  52. 52.
    Arbuckle MR, McClain MT, Rubertone MV et al (2003) Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med 349(16):1526–1533PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Stephanie C. Joachim
    • 1
  • Jan Reichelt
    • 1
  • Simone Berneiser
    • 1
  • Norbert Pfeiffer
    • 1
  • Franz H. Grus
    • 1
    Email author
  1. 1.Experimental Ophthalmology, Department of OphthalmologyJohannes Gutenberg UniversityMainzGermany

Personalised recommendations