Skip to main content

The specificity of disease-associated anti-fibrillarin autoantibodies compared with that of HgCl2-induced autoantibodies

Abstract

Autoantibodies against nucleolar components are a common serological feature of patients suffering from scleroderma, a collagen vascular autoimmune disease. An important target of these autoantibodies is a protein with an apparent molecular weight of 36 kDa and a pI value of 8.5, located in the dense fibrillar component of the nucleolus and therefore termed fibrillarin. Animal models in which abundant anti-nucleolar antibodies appear spontaneously have not yet been described; however, high levels of anti-fibrillarin antibodies can be induced by treating susceptible strains of mice with sub-toxic amounts of mercuric chloride. In this study, we have analysed the specificity of anti-fibrillarin autoantibodies of human and murine origin. Our results suggest that both species have similar, if not identical conformational epitopes that are the target of anti-fibrillarin autoantibodies; these epitopes require the presence of a 30-kDa fragment of the fibrillarin molecule. Post-translational modifications such as the dimethylation of arginines in the N terminus of the protein are not essential for antibody recognition.

This is a preview of subscription content, access via your institution.

Abbreviations

ANA:

Antinuclear autoantibodies

ANolA:

Antinucleolar autoantibodies

snoRNA:

small nucleolar RNA

snoRNP:

small nucleolar ribonucleoprotein

References

  1. Ritchie RF (1970) N. Engl. J. Med. 282: 1174–1178

    Google Scholar 

  2. Pinnas JL, Northway JD & Tan EM (1973) J. Immunol. 111: 996–1004

    Google Scholar 

  3. Bernstein RM, Steigerwald JC & Tan EM (1982) Clin. Exp. Immunol. 48: 43–51

    Google Scholar 

  4. Lischwe MA, Ochs RL, Reddy R, Cook RG, Yeoman LC, Tan EM, Reichlin M & Busch H (1985) J. Biol. Chem. 260: 14304–14310

    Google Scholar 

  5. Ochs RL, Lischwe M, Spohn WH & Busch H (1985) Biol. Cell 54: 123–134

    Google Scholar 

  6. Guiltinan MJ, Schelling ME, Ehtesham NZ, Thomas JC & Christensen ME (1988) Cell Biol. 46: 547–553

    Google Scholar 

  7. Goter Robinson CJ, Abraham AA & Balazs T (1984) Clin. Exp. Immunol. 58: 300–306

    Google Scholar 

  8. Goter Robinson CJ, Balazc T & Egorov IK (1986) Tox. Appl. Pharmacol. 86: 159–169

    Google Scholar 

  9. Mirtcheva J, Pfeiffer C, De Bruijn JA, Jaquesmart F & Gleichmann E (1989) Eur. J. Immunol. 19: 2257–2261

    Google Scholar 

  10. Reuter R, Tessars G, Vohr H-W, Gleichmann E & Lührmann R (1989) Proc. Natl. Acad. Sci. USA 86: 237–241

    Google Scholar 

  11. Hultman P, Eneström S, Pollard KM & Tan EM (1989) Clin. Exp. Immunol. 78: 470–477

    Google Scholar 

  12. Hultman P, Bell LJ, Eneström S & Pollard KM (1992) Clin. Immunol. Immunopathol. 65: 98–109

    Google Scholar 

  13. Hultman P, Eneström S & Skogh T (1989) J. Clin. Lab. Immunol. 29: 175–183

    Google Scholar 

  14. Habets WJ, de Rooij DJ, Salden MH, Verhagen AP, van Eekelen CA, van de Putte LB & van Venrooij WJ (1983) Clin. Exp. Immunol. 54: 265–276

    Google Scholar 

  15. Laemmli UK (1970) Nature 227: 680–685

    Google Scholar 

  16. Schagger H & von Jagow G (1987) Anal. Biochem. 166: 368–379

    Google Scholar 

  17. Towbin H, Staehelin T & Gordon (1979) Proc. Natl. Acad. Sci. USA 76: 5350–4354

    Google Scholar 

  18. Zeller R, Nyffenegger T & De Robertis E. M. (1983) Cell 32: 425–434

    Google Scholar 

  19. Lapeyre B, Mariottini P, Mathieu C, Ferrer P, Amaldi F, Amalric F & Caizergues-Ferrer M (1990) Mol. Cell. Biol. 10: 430–434

    Google Scholar 

  20. Stanley KK & Luzio JP (1984) EMBO J. 3: 1429–1434

    Google Scholar 

  21. Marston FAO (1987) In: Glover DM (Ed.) DNA cloning: A practical approach (pp. 59) Oxford: IRL Press

    Google Scholar 

  22. Cremer K, Premkumar R & Aaronson SA (1981) J. Virol. 38: 704–711

    Google Scholar 

  23. Radsak KD, Brücher KH & Georgatos SD (1991) Europ. J. Cell Biol. 54: 299–304

    Google Scholar 

  24. Christensen ME & Banker N (1992) Cell Biol. Internat. Rep. 16: 1119–1132

    Google Scholar 

  25. Saegusa J, Yamamoto S, Iwai H & Ueda K (1990) Ind. Hlth. 28: 21–30

    Google Scholar 

  26. Goldman M, Druet P & Gleichmann E (1991) Immunol. Today 12: 223–227

    Google Scholar 

  27. Ochel M, Vohr H-W, Pfeiffer C & Gleichmann E (1991) J. Immunol. 146: 3006–3011

    Google Scholar 

  28. van Vliet E, Uhrberg M, Stein C & Gleichmann E (1993) Int. Arch. Allergy Immunol. 101: 392–401

    Google Scholar 

  29. Kubicka-Muranyi M, Behmer O, Uhrberg M, Klonowski H, Bister J & Gleichmann E (1993) Int. J. Immunopharmac 15: 151–161

    Google Scholar 

  30. Mamula MJ, Lui R-H, Janeway CA & Hardin JA (1992) J. Immunol. 149: 789–795

    Google Scholar 

  31. Mamula MJ (1993) J. Exp. Med. 177: 567–571

    Google Scholar 

  32. Lehman PV, Sercarz EE, Forsthuber T, Dayan CM & Gammon G (1993) Immunol. Today 14: 203–208

    Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Lübben, B., Rottmann, N., Kubicka-Muranyi, M. et al. The specificity of disease-associated anti-fibrillarin autoantibodies compared with that of HgCl2-induced autoantibodies. Mol Biol Rep 20, 63–73 (1994). https://doi.org/10.1007/BF00996355

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00996355

Key words

  • autoimmunity
  • anti-nucleolar autoantibodies
  • scleroderma