Skip to main content

Advertisement

Log in

Analysis of IgG antibody patterns against retinal antigens and antibodies to α-crystallin, GFAP, and α-enolase in sera of patients with “wet” age-related macular degeneration

  • Review Article
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Background

The aim of this study was to compare the IgG antibody patterns against retinal antigens in sera of patients with age-related macular degeneration (AMD) and healthy subjects to learn more about possible immunological aspects of this disease and to identify some of the most important antigens.

Methods

Sera of 140 patients were analyzed: healthy volunteers (CO, n=101) and patients with “wet” age-related macular degeneration (AMD, n=39). The sera were tested against western blots of bovine retinal antigens. The IgG antibody patterns were analyzed by multivariate statistical techniques and some antigens were identified via LC-MS/MS.

Results

All patients showed complex patterns of IgG antibodies against retinal antigens. The discriminant analysis revealed a statistical significant difference between the antibody profiles of the AMD and the CO group (P=0.000023). Not only up-regulations of antigen-antibody-reactivities in the AMD group at some molecular weight ranges, e.g. at 46 and 52 kDa, could be seen, but also down-regulations, e.g. at 18 and 36 kDa. The 18 kDa antigen band was identified as αB-crystallin, the band at 46 kDa as α-enolase, and one at 52 kDa as glial fibrillary acidic protein.

Conclusions

We could demonstrate that both groups (wet AMD and CO) show complex IgG antibody patterns against retinal antigens, which are highly specific for each group. This provides further hints for the immunological basis of the disease. These changes in the antibody profiles in “wet” AMD could represent a secondary response to retinal damage or can play a causative role in the disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Evans JR (2001) Risk factors for age-related macular degeneration. Prog Retin Eye Res 20(2):227–253

    Article  PubMed  CAS  Google Scholar 

  2. O’Malley P (1989) Retina and intraocular tumors. In: Vaughan D, Asbury T, Tabbara KF (eds) General ophthalmology, 12th edn. Prentice-Hall, New York

  3. Hyman L (1992) Epidemiology. In: Hampton GR, Nelson PT (eds) Age-related macular degeneration. Raven, New York

    Google Scholar 

  4. Cavallerano AA (1997) Age-related macular degeneration. In: Cavallerano AA, Guntner RK, Oshinskie LJ (eds) Macular disorders. Butterworth-Heinemann, Newton

    Google Scholar 

  5. Kincaid MC (1992) Pathology of AMD. In: Hampton GR, Nelson PT (eds) Age-related macular degeneration. Raven, New York

    Google Scholar 

  6. Klein R, Peto T, Bird A, Vannewkirk MR (2004) The epidemiology of age-related macular degeneration. Am J Ophthalmol 137(3):486–495

    Article  PubMed  Google Scholar 

  7. Tomany SC, Wang JJ, Van Leeuwen R et al (2004) Risk factors for incident age-related macular degeneration: pooled findings from 3 continents. Ophthalmology 111(7):1280–1287

    Article  PubMed  Google Scholar 

  8. Penfold PL, Provis JM, Furby JH et al (1990) Autoantibodies to retinal astrocytes associated with age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 228(3):270–274

    Article  PubMed  CAS  Google Scholar 

  9. Gurne DH, Tso MO, Edward DP, Ripps H (1991) Anti-retinal antibodies in serum of patients with age-related macular degeneration. Opthalmology 98(5):602–607

    PubMed  CAS  Google Scholar 

  10. Dumonde DC, Kasp-Grochowska E, Graham E et al (1982) Anti-retinal autoimmunity and circulating immune complexes in patients with retinal vasculitis. Lancet 2(8302):787–792

    Article  PubMed  CAS  Google Scholar 

  11. Adamus G, Ren G, Weleber RG (2004) Autoantibodies against retinal proteins in paraneoplastic and autoimmune retinopathy. BMC Ophthalmol 4(1):5

    Article  PubMed  Google Scholar 

  12. Savchenko MS, Bazhin AV, Shifrina ON et al (2003) Antirecoverin autoantibodies in the patient with non-small cell lung cancer but without cancer-associated retinopathy. Lung Cancer 41(3):363–367

    Article  PubMed  Google Scholar 

  13. Heckenlively JR, Fawzi AA, Oversier J et al (2000) Autoimmune retinopathy: patients with antirecoverin immunoreactivity and panretinal degeneration. Arch Ophthalmol 118(11):1525–1533

    PubMed  CAS  Google Scholar 

  14. Galbraith GM, Emerson D, Fudenberg HH et al (1986) Antibodies to neurofilament protein in retinitis pigmentosa. J Clin Invest 78(4):865–869

    PubMed  CAS  Google Scholar 

  15. Zimmermann CW, Grus FH, Dux R (1995) Multivariate statistical comparison of autoantibody-repertoires (western blots) by discriminant analysis. Electrophoresis 16(6):941–947

    Article  PubMed  CAS  Google Scholar 

  16. 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):106–113

    Article  PubMed  CAS  Google Scholar 

  17. Singer HS, Loiselle CR, Lee O et al (2003) Anti-basal ganglia antibody abnormalities in Sydenham chorea. J Neuroimmunol 136(1–2):154–161

    Article  PubMed  CAS  Google Scholar 

  18. Singer HS, Loiselle CR, Lee O et al (2004) Anti-basal ganglia antibodies in PANDAS. Mov Disord 19(4):406–415

    Article  PubMed  Google Scholar 

  19. Grus FH, Joachim SC, Hoffmann EM, Pfeiffer N (2004) Complex autoantibody repertoires in patients with glaucoma. Mol Vis 10:132–137

    PubMed  CAS  Google Scholar 

  20. Joachim SC, Grus FH, Pfeiffer N (2003) Analysis of autoantibody repertoires in sera of patients with glaucoma. Eur J Ophthalmol 13(9–10):752–758

    PubMed  CAS  Google Scholar 

  21. 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):817–823

    Article  PubMed  CAS  Google Scholar 

  22. 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):968–976

    Article  PubMed  Google Scholar 

  23. Chen H, Wu L, Pan S, Wu DZ (1993) An immunologic study on age-related macular degeneration. Yan Ke Xue Bao 9(3):113–120

    PubMed  CAS  Google Scholar 

  24. Gu X, Meer SG, Miyagi M et al (2003) Carboxyethylpyrrole protein adducts and autoantibodies, biomarkers for age-related macular degeneration. J Biol Chem 278(43):42027–42035

    Article  PubMed  CAS  Google Scholar 

  25. Seddon JM, Gensler G, Milton RC et al (2004) Association between C-reactive protein and age-related macular degeneration. Jama 291(6):704–710

    Article  PubMed  CAS  Google Scholar 

  26. Anderson DH, Mullins RF, Hageman GS, Johnson LV (2002) A role for local inflammation in the formation of drusen in the aging eye. Am J Ophthalmol 134(3):411–431

    Article  PubMed  CAS  Google Scholar 

  27. Patel N, Ohbayashi M, Nugent AK et al (2005) Circulating anti-retinal antibodies as immune markers in age-related macular degeneration. Immunology 115(3):422–430

    Article  PubMed  CAS  Google Scholar 

  28. Luiz JE, Lee AG, Keltner JL et al (1998) Paraneoplastic optic neuropathy and autoantibody production in small-cell carcinoma of the lung. J Neuroophthalmol 18(3):178–181

    PubMed  CAS  Google Scholar 

  29. Jankowska R, Witkowska D, Porebska I et al (2004) Serum antibodies to retinal antigens in lung cancer and sarcoidosis. Pathobiology 71(6):323–328

    Article  PubMed  CAS  Google Scholar 

  30. Brinkman CJ, Pinckers AJ, Broekhuyse RM (1980) Immune reactivity to different retinal antigens in patients suffering from retinitis pigmentosa. Invest Ophthalmol Vis Sci 19(7):743–750

    PubMed  CAS  Google Scholar 

  31. Kumar M, Gupta RM, Nema HV (1983) Role of autoimmunity in retinitis pigmentosa. Ann Ophthalmol 15(9):838–840

    PubMed  CAS  Google Scholar 

  32. Lewis GP, Fisher SK (2003) Up-regulation of glial fibrillary acidic protein in response to retinal injury: its potential role in glial remodeling and a comparison to vimentin expression. Int Rev Cytol 230:263–290

    Article  PubMed  CAS  Google Scholar 

  33. Norgren N, Sundstrom P, Svenningsson A et al (2004) Neurofilament and glial fibrillary acidic protein in multiple sclerosis. Neurology 63(9):1586–1590

    PubMed  CAS  Google Scholar 

  34. 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):573–583

    Article  PubMed  CAS  Google Scholar 

  35. 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):115–125

    Article  PubMed  Google Scholar 

  36. Lam TT, Kwong JM, Tso MO (2003) Early glial responses after acute elevated intraocular pressure in rats. Invest Ophthalmol Vis Sci 44(2):638–645

    Article  PubMed  Google Scholar 

  37. Madigan MC, Penfold PL, Provis JM et al (1994) Intermediate filament expression in human retinal macroglia. Histopathologic changes associated with age-related macular degeneration. Retina 14(1):65–74

    Article  PubMed  CAS  Google Scholar 

  38. Guidry C, Medeiros NE, Curcio CA (2002) Phenotypic variation of retinal pigment epithelium in age-related macular degeneration. Invest Ophthalmol Vis Sci 43(1):267–273

    PubMed  Google Scholar 

  39. Wu KH, Madigan MC, Billson FA, Penfold PL (2003) Differential expression of GFAP in early v late AMD: a quantitative analysis. Br J Ophthalmol 87(9):1159–1166

    Article  PubMed  CAS  Google Scholar 

  40. Singh VK, Warren R, Averett R, Ghaziuddin M (1997) Circulating autoantibodies to neuronal and glial filament proteins in autism. Pediatr Neurol 17(1):88–90

    Article  PubMed  CAS  Google Scholar 

  41. Klemenz R, Frohli E, Steiger RH et al (1991) Alpha B-crystallin is a small heat shock protein. Proc Natl Acad Sci USA 88(9):3652–3656

    Article  PubMed  CAS  Google Scholar 

  42. Stoevring B, Vang O, Christiansen M (2005) (alpha)B-crystallin in cerebrospinal fluid of patients with multiple sclerosis. Clin Chim Acta 356(1–2):95–101

    Article  PubMed  CAS  Google Scholar 

  43. Garcia-Castineiras S, Andino Moreno ME, Perez R, Vazquez LA (1993) Antibodies to lens crystallins after endocapsular cataract surgery. P R Health Sci J 12(2):123–128

    PubMed  CAS  Google Scholar 

  44. Sandberg HO, Closs O (1979)The humoral immune response to alpha, beta and gamma crystallins of the human lens. Scand J Immunol 10(6):549–554

    Article  PubMed  CAS  Google Scholar 

  45. Iida H, Yahara I (1985) Yeast heat-shock protein Mr 48,000 is a isoprotein of enolase. Nature 315:688–690

    Article  CAS  Google Scholar 

  46. Pratesi F, Moscato S, Sabbatini A et al (2000) Autoantibodies specific for alpha-enolase in systemic autoimmune disorders. J Rheumatol 27(1):109–115

    PubMed  CAS  Google Scholar 

  47. Wakui H, Imai H, Komatsuda A, Miura AB (1999) Circulating antibodies against alpha-enolase in patients with primary membranous nephropathy (MN). Clin Exp Immunol 118(3):445–450

    Article  PubMed  CAS  Google Scholar 

  48. Dot C, Guigay J, Adamus G (2005) Anti-alpha-enolase antibodies in cancer-associated retinopathy with small cell carcinoma of the lung. Am J Ophthalmol 139(4):746–747

    Article  PubMed  CAS  Google Scholar 

  49. Weleber RG, Watzke RC, Shults WT et al (2005) Clinical and electrophysiologic characterization of paraneoplastic and autoimmune retinopathies associated with antienolase antibodies. Am J Ophthalmol 139(5):780–794

    Article  PubMed  CAS  Google Scholar 

  50. Thirkill CE, Tait RC, Tyler NK et al (1992) The cancer-associated retinopathy antigen is a recoverin-like protein. Invest Ophthalmol Vis Sci 33(10):2768–2772

    PubMed  CAS  Google Scholar 

  51. Ren G, Adamus G (2004) Cellular targets of anti-alpha-enolase autoantibodies of patients with autoimmune retinopathy. J Autoimmun 23(2):161–167

    Article  PubMed  CAS  Google Scholar 

  52. Bazhin AV, Schadendorf D, Philippov PP, Eichmuller SB (2006) Recoverin as a cancer-retina antigen. Cancer Immunol Immunother pp 1–7

  53. Thirkill CE (1997) Experimental, cancer-induced retinopathy. Ocul Immunol Inflamm 5(1):55–65

    Article  PubMed  CAS  Google Scholar 

  54. Avrameas S (1991) Natural autoantibodies: from ‘horror autotoxicus’ to ‘gnothi seauton’. Immunol Today 12(5):154–159

    PubMed  CAS  Google Scholar 

  55. Lacroix-Desmazes S, Kaveri SV, Mouthon L et al (1998) Self-reactive antibodies (natural autoantibodies) in healthy individuals. J Immunol Methods 216(1–2):117–137

    Article  PubMed  CAS  Google Scholar 

  56. Ambati J, Anand A, Fernandez S et al (2003) An animal model of age-related macular degeneration in senescent Ccl-2- or Ccr-2-deficient mice. Nat Med 9(11):1390–1397

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Franz H. Grus.

Additional information

Supported by MAIFOR and “Schwerpunkt Praeventive Medizin” University of Mainz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Joachim, S.C., Bruns, K., Lackner, K.J. et al. Analysis of IgG antibody patterns against retinal antigens and antibodies to α-crystallin, GFAP, and α-enolase in sera of patients with “wet” age-related macular degeneration. Graefe's Arch Clin Exp Ophthalmol 245, 619–626 (2007). https://doi.org/10.1007/s00417-006-0429-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-006-0429-9

Keywords

Navigation