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High incidence of antibodies to lens proteins in sera from patients with uveitis

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An Erratum to this article was published on 21 February 2007

Abstract

Background

Uveitis is an intraocular inflammatory disease in which autoimmune reactions have been discussed in playing an important role. Many data in this respect derived from the animal model of “experimental autoimmune uveitis”, where several organ-specific autoantigens have been described such as the retinal S-antigen and the interphotoreceptor retinoid-binding protein. However, their diagnostic and pathogenic role in humans has been controversially discussed. In recent studies, the possible relevance of βB1-crystallin, present in lens and ciliary body, has been outlined. We, therefore, wanted to analyse whether sera from patients with uveitis might contain antibodies to lens proteins

Methods

Human lenses from cadaveric eyes were shock frozen, homogenized, and resuspended. The resulting suspension (human lens protein fraction - HLPF) was analyzed for antigenicity by ELISA and Western blotting with patients’ sera. A total of 165 patients with uveitis, 54 patients with scleritis and episcleritis, 56 patients with other eye diseases, and 112 healthy blood donors were studied.

Results

Twenty-six (49%) of the 53 patients with anterior uveitis, 17 (32%) of the 53 patients with intermediate uveitis and 7 (22%) of 32 patients with posterior uveitis reacted in the ELISA with the HLPF. Antibodies to lens antigens were detected in one-third of patients with panuveitis and retinal vasculitis. In contrast, only 12% of the healthy blood donors were positive in the ELISA. The number of patients with an autoimmune response to α-crystallins in Western blot predominated in all investigated groups.

Conclusions

These data indicate that antibodies to lens proteins occur in a high incidence in sera from patients with uveitis. Forty-nine percent of the patients with anterior uveitis and only 12% of healthy controls were positive in the ELISA. In our groups of patients and controls the autoantibodies reacted in the Western blot predominantly with α-crystallin. Further studies are required to analyze in more detail the clinical and etiopathogenetic relevance of the antilens antibodies in uveitis.

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References

  1. Abrahams WI, Gregerson DS (1982) Longitudinal study of serum antibody responses to retinal antigens in acute ocular toxoplasmosis. Am J Ophthalm 93:224–231

    CAS  Google Scholar 

  2. Adamus G, Chang CC (2002) Experimental autoimmune uveitides: multiple antigens, diverse diseases. Int Rev Immunol 21:209–229

    Article  PubMed  CAS  Google Scholar 

  3. Annunziata O, Pande A, Pande J et al (2005) Oligomeristion and phase transitions in aqueous solutions of native and truncated human βB1-crystallin. Biochem 44:1316–1328

    Article  CAS  Google Scholar 

  4. Augusteyn RC (2004) α-crystallin: a review of its structure and function. Clin Exp Optom 87:356–366

    Article  PubMed  Google Scholar 

  5. David LL, Lampi KJ, Lund AL et al (1996) The sequence of human βB1-crystallin cDNA allows mass spectrometric detection of βB1 protein missing portions of its N-terminal extension. J Biol Chem 271:4273–4279

    Article  PubMed  CAS  Google Scholar 

  6. Denis HM, Broks DE, Alleman AR et al (2003) Detection of anti-lens crystalline antibody in dogs with and without cataracts. Vet Opthalmol 6(4):321–327

    Article  CAS  Google Scholar 

  7. D’Ermo F, Secchi AG, Mancini B et al (1978) Immunopathology of the lens. I. Rb Efflux and protein leakage from normal lenses exposed to unrelated antigen-antibody interactions. Ophthalmologica 176:164–169

    Google Scholar 

  8. D’Ermo F, Secchi AG, Mancini B et al (1978) Immunopathology of the lens. II. Rb Efflux and protein leakage from normal lenses exposed to antilens und antiuveoretina antibodies. Ophthalmologica 176:230–234

    PubMed  CAS  Google Scholar 

  9. D’Ermo F, Secchi AG, Segato T et al (1978) Immunopathology of the lens. III. The effect of experimental allergic uveitis on the cation balance in the lens. Ophthalmologica 176:258–261

    Article  PubMed  CAS  Google Scholar 

  10. de Smet MD, Bitar G, Roberge FG et al (1993) Human S-antigen: presence of multiple immunogenic and immunopathogenic sites in the Lewis rat. J Autoimmunity 6:587–599

    Article  Google Scholar 

  11. Dighiero G, Guilbert B, Avrameas S (1982) Naturally occurring antibodies against nine common antigens in human sera. II. High incidence of monoclonal Ig exhibiting antibody activity against actin and tubulin and sharing antibody specificity with natural antibodies. J Immunol 128:2788–2792

    PubMed  CAS  Google Scholar 

  12. Dighiero G, Lymberi P, Holmberg D et al (1985) High frequency of natural autoantibodies in normal new born mice. J Immunol 134:765–771

    PubMed  CAS  Google Scholar 

  13. Dua HH, Lee RH, Lolley RN et al (1992) Induction of experimental autoimmune uveitis by the retinal photoreceptor cell protein, phosducin. Curr Eye Res 11:107–111

    PubMed  Google Scholar 

  14. Elschnig A (1910) Studien zur sympathischen Ophthalmie: die antigen Wirkung des Augenpigmentes. Graefes Arch Ophthalmol 76:509–546

    Article  Google Scholar 

  15. Forrester JV, Stott DI, Hercus KM (1989) Naturally occurring antibodies to bovine and human retinal S-antigen: a comparison between uveitis patients and healthy volunteers. Br J Ophthalmol 73:155–159

    PubMed  CAS  Google Scholar 

  16. Fox GM, Kuwabara T, Wiggert B et al (1987) Experimental autoimmune uveoretinitis (EAU) induced by retinal interphotoreceptor retinoid-binding protein (IRBP): differences between EAU induced by IRBP and by S-antigen. Clin Immunol Immunopathol 43:256–264

    Article  PubMed  CAS  Google Scholar 

  17. Gery I, Chanaud NP, Anglade E (1994) Recoverin is highly uveitogenic in Lewis rats. Invest Ophthalmol Vis Sci 35:3342–3345

    PubMed  CAS  Google Scholar 

  18. Goldschmidt L, Goldbaum M, Walker SM et al (1982) The immune response to homologous lens crystallin. I. Antibody production after lens injury. J Immunol 129:1652–1657

    PubMed  CAS  Google Scholar 

  19. Goldschmidt L, Goldbaum M, Walker SM et al (1982) The immune response to homologous lens crystallin. II. A model of ocular inflammation involving eye injuries at separate times. J Immunol 129:1658–1662

    PubMed  CAS  Google Scholar 

  20. Gregerson DS, Abrahams IW, Thirkill CE (1981) Serum antibody levels of uveitis patients to bovine retinal antigens. Invest Ophthalmol Vis Sci 21:669–680

    PubMed  CAS  Google Scholar 

  21. Guilbert B, Dighiero G, Avrameas S (1982) Naturally occurring antibodies against nine common antigens in human sera. I. Detection, isolation and characterization. J Immunol 128:2779–2787

    PubMed  CAS  Google Scholar 

  22. Holmberg D, Forgren S, Ivars F et al (1984) Reactions among IgM antibodies derived from normal, neonatal mice. Eur J Immunol 14:435–441

    Article  PubMed  CAS  Google Scholar 

  23. Ibaraki N, Lin LR, Dang L et al (1997) Anti-β-crystallin antibodies (mouse) or sera from humans with age-related cataract are cytotoxic for lens epithelial cells in culture. Exp Eye Res 64:229–238

    Article  PubMed  CAS  Google Scholar 

  24. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685

    Article  PubMed  CAS  Google Scholar 

  25. Lampi KJ, Ma Z, Shih M et al (1997) Sequence analysis of βA3, βB3 and βA4 crystallins completes the identification of the major proteins in young human lens. J Biol Chem 272:2268–2275

    Article  PubMed  CAS  Google Scholar 

  26. Luntz M (1968) Antiuveal and antilens antibodies in uveitis and their significance. Exp Eye Res 7:561–569

    Article  PubMed  CAS  Google Scholar 

  27. Merck KB et al (1993) Characterisation of anti-crystallin antibodies in patients with cataract. Mol Biol Rep 17(2):93–99

    Article  PubMed  CAS  Google Scholar 

  28. Misra RN, Rahi AHS, Morgan G (1977) Immunopathology of the lens. II. Humoral and cellular immune responses to homologous lens antigens and their roles in ocular inflammation. Br J Ophthalmol 61:285–296

    PubMed  CAS  Google Scholar 

  29. Nissen SH, Andersen P, Andersen HMK (1981) Antibodies to lens antigens in cataract and after cataract surgery. Br J Ophthalmol 65:63–66

    PubMed  CAS  Google Scholar 

  30. Nussenblatt RB (2004) Elements of the immune system and concepts of intraocular inflammatory disease pathogenesis. In: Nussenblatt RB, Whitcup SM (eds) Uveitis, fundamentals and clinical practice. Elsevier-Mosby, Philadelphia, p 30

    Google Scholar 

  31. Nussenblatt RB (1990) The natural history of uveitis. Int Ophthalmol 14:303–308

    Article  PubMed  CAS  Google Scholar 

  32. Patel M, Shine B, Murray PI (1990) Antilens antibodies in cataract and inflammatory eye disease: an evaluation of a new technique. Int Ophthalmol 14:97–100

    Article  PubMed  CAS  Google Scholar 

  33. Rahi AHS, Misra RN, Morgan G (1977) Immunopathology of the lens. I. Humoral and cellular immune responses to heterologous lens antigens and their roles in ocular inflammation. Br J Ophthalmol 61:164–176

    PubMed  CAS  Google Scholar 

  34. Rahi AHS, Misra RN, Morgan G (1977) Immunopathology of the lens. III. Humoral and cellular immune responses to autologous lens antigens and their roles in ocular inflammation. Br J Ophthalmol 61:371–379

    PubMed  CAS  Google Scholar 

  35. Singh DP, Guru SC, Kukuchi T (1995) Autoantibodies against β-crystallins induce lens epithelial cell damage and cataract formation in mice. J Immunol 155:993–999

    PubMed  CAS  Google Scholar 

  36. Stempel D, Sandusky H, Lampi K et al (2003) Beta B1-crystallin: Identification of a candidate ciliary body uveitis antigen. Invest Ophthmol Vis Sci 44:203–209

    Article  Google Scholar 

  37. Wacker WB, Donoso LA, Kalsow CM et al (1977) Experimental allergic uveitis: isolation, characterization and localization of a soluble uveitopathogenic antigen from bovine retina. J Immunol 119:1949–1958

    PubMed  CAS  Google Scholar 

  38. Wirostko E, Spalter HF (1967) Lens-induced uveitis. Arch Ophthalmol 78:1–7

    PubMed  CAS  Google Scholar 

  39. Yamaki K, Kondo I, Nakamura H et al (2000) Ocular and extraocular inflammation induced by immunization of tyrosinase related protein 1 and 2 in Lewis rats. Exp Eye Res 71:361–369

    Article  PubMed  CAS  Google Scholar 

  40. Zierhut M, Schlote T, Tomida I, Stiemer R (2000) Immunology of uveitis and ocular allergy. Acta Ophthalmol Scand Suppl 230 (Suppl) 22–25

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. University Eye Hospital, Schleichstr. 12-16, 72076, Tuebingen, Germany

    Doycheva Deshka & Zierhut Manfred

  2. Department of Internal Medicine II, University of Tuebingen, Otfried-Mueller Str. 10, 72076, Tuebingen, Germany

    Preuss Beate & Klein Reinhild

Authors
  1. Doycheva Deshka
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  2. Preuss Beate
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  3. Klein Reinhild
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  4. Zierhut Manfred
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Corresponding author

Correspondence to Zierhut Manfred.

Additional information

D. Doycheva was supported by a grant from Alexander von Humboldt Foundation. B. Preuss was supported by the Deutsche Forschungsgemeinschaft (GRK 794).

An erratum to this article can be found at http://dx.doi.org/10.1007/s00417-007-0539-z

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Deshka, D., Beate, P., Reinhild, K. et al. High incidence of antibodies to lens proteins in sera from patients with uveitis. Graefe's Arch Clin Exp Ophthalmol 245, 683–688 (2007). https://doi.org/10.1007/s00417-006-0407-2

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  • DOI: https://doi.org/10.1007/s00417-006-0407-2

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