Journal of Clinical Immunology

, Volume 4, Issue 3, pp 209–219 | Cite as

Antibodies to heterogeneous nuclear ribonucleoproteins in sera from patients with rheumatic autoimmune diseases

  • Moncef Zouali
  • André Eyquem
Original Articles
Accepted:

Abstract

Ribonucleoprotein (RNP) particles sedimenting at 40 S in sucrose gradients were prepared from calf thymus nuclei. They were identified as heterogeneous nuclear RNP (hnRNP) on the basis of size, electron microscopic examination, buoyant density, and protein electrophoretic patterns. Sera from patients with systemic lupus erythematosus, rheumatoid arthritis, and mixed connective tissue disease were found to interact with hnRNP by counter-immunoelectrophoresis and enzyme-linked immunosorbent assay (ELISA). Small nuclear RNP (snRNP) were purified by immunoaffinity using a monoclonal anti-snRNP antibody immobilized on Sepharose beads. Inhibition of the ELISA assay for snRNP with anti-hnRNP Fab fragments and cross-over experiments revealed that the autoantibodies detected in human sera recognize common epitopes present on snRNP and hnRNP.

Key words

Antibodies to ribonucleoproteins autoimmunity rheumatic diseases 
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Reichlin M: Current perspectives on serological reactions in SLE patients. Clin Exp Immunol 44:1–10, 1981Google Scholar
  2. 2.
    Sharp GC, Irvin WS, Tan EM, Gould RG, Holman HR: Mixed connective tissue disease an apparently distinct rheumatic syndrome associated with a specific antibody to an extractable nuclear antigen (ENA). Am J Med 52:148–159, 1972Google Scholar
  3. 3.
    Parker MD: Ribonucleoprotein antibodies: Frequency and clinical significance in systemic lupus erythematosus, scleroderma and mixed connective tissue disease. J Lab Clin Med 82:769–775, 1973Google Scholar
  4. 4.
    Reichlin M: Problems in differentiating S.L.E. and mixed connective tissue disease. N Engl J Med 295:1194–1195, 1976Google Scholar
  5. 5.
    Sharp GC, Irvin WS, May CM, Holman HR, Duffie FC, Hess EV, Schmid FR: Association of antibodies to ribonucleoprotein and Sm antigens with mixed connective-tissue disease, systemic lupus erythematosus (SLE) and other rheumatic diseases. N Engl J Med 295:1149–1154, 1976Google Scholar
  6. 6.
    Alarcon-Segovia D, Ruiz-Arguelles A, Fishbein E: Antibody to nuclear ribonucleoprotein penetrates live human mononuclear cells through Fc receptors. Nature 271:67–69, 1978Google Scholar
  7. 7.
    Lerner MR, Steitz JA: Antibodies to small nuclear RNAs complexed with proteins are produced by patients with systemic lupus erythematosus. Proc Natl Acad Sci USA 76:5495–5499, 1979Google Scholar
  8. 8.
    Lerner MR, Boyle JA, Mount SM, Wolin SL, Steitz JA: Are snRNPs involved in splicing? Nature 283:220–224, 1980Google Scholar
  9. 9.
    Jacob M, Devilliers G, Fuchus JP, Gallinaro H, Gattoni R, Judes C, Stevenin J: Isolation and structure of the ribonucleoprotein fibrils containing heterogenous nuclear RNA. Cell Nucleus 8:193–246, 1981Google Scholar
  10. 10.
    Busch H, Reddy R, Rothblum L, Choi YC: SnRNAs, snRNPs and RNA processing. Annu Rev Biochem 51:617–654, 1982Google Scholar
  11. 11.
    Billings PB, Allen RW, Jensen FC, Hoch SO: Anti-RNP monoclonal antibodies derived from a mouse strain with lupus-like autoimmunity. J Immunol 128:1176–1180, 1982Google Scholar
  12. 12.
    Zouali M, Drouhet E, Eyquem A: Longitudinal evaluation of autoantibodies in chronic mucocultaneous candidiasis. Mycopathologia (in press), 1984Google Scholar
  13. 13.
    Eilat D, Laskov R: Production of antibody by hybridoma cells: Purification from mixed immunoglobulin products. Mol Immunol 18:589–595, 1981Google Scholar
  14. 14.
    Goodvin GH, Woodhead L, Johns EW: The presence of high mobility group non-histone chromatin proteins in isolated nucleosomes. FEBS Lett 73:85–88, 1977Google Scholar
  15. 15.
    Samarina OP, Lukanidin EM, Molnar J, Georgiev GP: Structural organization of nuclear complexes containing DNA-like RNA. J Mol Biol 33:251–263, 1968Google Scholar
  16. 16.
    Karn J, Vidali G, Boffa CL, Allfrey VG: Characterization of the non-histone nuclear proteins associated with rapidly labeled heterogenous nuclear RNA. J Biol Chem 252:7307–7322, 1977Google Scholar
  17. 17.
    Martin RG, Ames BN: A method for determining the sedimentation behaviour of enzymes. J Biol Chem 236:1372–1379, 1961Google Scholar
  18. 18.
    Maundrell K, Scherrer K: Characterization of pre-messenger containing nuclear ribonucleoprotein particles from avian Erythroblasts. Eur J Biochem 99:225–238, 1979Google Scholar
  19. 19.
    Cambiaso CL, Goffinet A, Vaerman JP, Heremans JF: Glutaraldehyde activated aminohexyl derivative of Sepharose-4B as a new versatile immuno-adsorbant. Immunochemistry 12:273–278, 1975Google Scholar
  20. 20.
    Laemeli UF: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685, 1970Google Scholar
  21. 21.
    Lowry OH, Rosebrough NJ, Farr AL, Randall PJ: Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275, 1951Google Scholar
  22. 22.
    Burton K: A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of desoxyribonucleic acid. Biochemistry 62:315–323, 1956Google Scholar
  23. 23.
    Dische Z: Color reactions of nucleic acid components.In The Cell Nucleus, E Chargaff, JN Davidson (eds). New York, Academic Press, 1955, pp 285–305Google Scholar
  24. 24.
    Stevenin J, Gattoni R, Devilliers G, Jacob M: Rearrangements in the course of ribonuclease hydrolysis of premessenger ribonucleoproteins. Eur J Biochem 95:593–606, 1979Google Scholar
  25. 25.
    Mirault ME, Scherrer K: Isolation of preribosomes from Hela cells and their characterization by electrophoresis on uniform and exponential-gradient-polyacrylamide gels. Eur J Biochem 23:372–386, 1971Google Scholar
  26. 26.
    Spirin AS: Informosomes. Eur J Biochem 10:20–35, 1969Google Scholar
  27. 27.
    Mattioli M, Reichlin M: Physical association of two nuclear antigens and mutual occurrence of their antibodies: The relationship of the Sm and RNA protein (Mo) systems in SLE sera. J Immunol 110:1318–1324, 1973Google Scholar
  28. 28.
    White PJ, Hoch SO: Definition of the antigenic polypeptides in the Sm and RNP ribonucleoprotein complexes. Biochem Biophys Res Commun 102:365–371, 1981Google Scholar
  29. 29.
    Zouali M, Eyquem A: Expression of anti-idiotypic clones against auto-anti-DNA antibodies in normal individuals. Cell Immunol 76:137–147, 1983Google Scholar
  30. 30.
    Douvas A: Autoantibodies occurring in two different rheumatic diseases react with the same nuclear ribonucleoprotein particles. Proc Natl Acad Sci USA 79:5401–5405, 1982Google Scholar
  31. 31.
    Tanako M, Agris PF, Sharp GC: Purification and biochemical characterization of nuclear ribonucleoprotein antigen using purified antibody from serum of a patient with mixed connective tissue disease. J Clin Invest 65:1449–1456, 1980Google Scholar
  32. 32.
    Buchanan RRC, Venables PJW, Morgan A, Staines NA, Smith PR, Maini RN: Separation of two molecular species of Sm antigen by affinity chromatography with murine monoclonal and human anti-nuclear antibodies. Clin Exp Immunol 51:8–16, 1983Google Scholar
  33. 33.
    Jonsson J, Norberg R: Some functional properties of the RNP nucleoplasmic antigen. Scand J Immunol 12:119–127, 1980Google Scholar
  34. 34.
    Boyer C, Cohen PL, Eisenberg RA: Quantitation of the Sm nuclear antigen. Arth Rheum 25:S22, 1982Google Scholar
  35. 35.
    Yang VW, Lerner MR, Steitz JA, Flint SJ: A small nuclear ribonucleoprotein is required for splicing of adenoviral early RNA sequences. Proc Natl Acad Sci USA 78:1371–1375, 1981Google Scholar
  36. 36.
    Sharp GC, Irvin WS, Laroqie RL, Velez C, Daly V, Kaiser AD, Holman HR: Association of auto-antibodies to different nuclear antigens with clinical patterns of rheumatic disease and responsiveness to therapy. J Clin Invest 50:350–359, 1971Google Scholar
  37. 37.
    Nortman DD, Kurata N, Tan EM: Profiles of antinuclear antibodies in systemic rheumatic diseases. Ann Intern Med 83:464–469, 1975Google Scholar

Copyright information

© Plenum Publishing Corporation 1984

Authors and Affiliations

  • Moncef Zouali
    • 1
  • André Eyquem
    • 1
  1. 1.Service D'Immunohématologie et D'ImmunopathologieInstitut PasteurParis CEDEX 15France

Personalised recommendations