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The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1985 Feb;75(2):580–587. doi: 10.1172/JCI111734

Autoimmune sera reactive with Sm antigen contain high levels of RNP-like antibodies.

W H Reeves, D E Fisher, R G Lahita, H G Kunkel
PMCID: PMC423533  PMID: 3973019

Abstract

Ribonucleoprotein particles containing Sm antigen were separated from particles containing both Sm and RNP antigens by ion-exchange chromatography to study the recognition of these antigens by autoimmune sera. By using the separated antigens, anti-Sm and/or anti-RNP antibodies were detected in approximately 60% of sera from systemic lupus erythematosus patients by both enzyme-linked immunosorbent assay and immunoprecipitation of radiolabeled antigens followed by analysis on sodium dodecyl sulfate-polyacrylamide gels. These antibodies were detected in 30% of the same sera using the standard passive hemagglutination technique. Competition experiments demonstrated that all of the sera tested that contained anti-Sm antibodies also had anti-RNP-like reactivity. This latter reactivity usually represented 80% or more of the total Sm and RNP binding activity in lupus sera. The binding to RNP-like determinants by several of the sera was uniquely resistant to treatment of the antigen with snake venom exonuclease. These studies indicate that humoral immunity against Sm and RNP antigens in systemic lupus erythematosus is directed primarily against a single type of ribonucleoprotein particle in which the two antigens are physically associated. The specific binding to a single type of ribonucleoprotein particle suggests that this particle may be especially immunogenic and that it might play an important role in induction of the humoral immune response to Sm and RNP.

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Selected References

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  1. Conner G. E., Nelson D., Wisniewolski R., Lahita R. G., Blobel G., Kunkel H. G. Protein antigens of the RNA-protein complexes detected by anti-SM and anti-RNP antibodies found in serum of patients with systemic lupus erythematosus and related disorders. J Exp Med. 1982 Nov 1;156(5):1475–1485. doi: 10.1084/jem.156.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Douvas A. S., Achten M., Tan E. M. Identification of a nuclear protein (Scl-70) as a unique target of human antinuclear antibodies in scleroderma. J Biol Chem. 1979 Oct 25;254(20):10514–10522. [PubMed] [Google Scholar]
  3. Fisher D. E., Conner G. E., Reeves W. H., Blobel G., Kunkel H. G. Synthesis and assembly of human small nuclear ribonucleoproteins generated by cell-free translation. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6356–6360. doi: 10.1073/pnas.80.20.6356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Fisher D. E., Reeves W. H., Conner G. E., Blobel G., Kunkel H. G. Pulse labeling of small nuclear ribonucleoproteins in vivo reveals distinct patterns of antigen recognition by human autoimmune antibodies. Proc Natl Acad Sci U S A. 1984 May;81(10):3185–3189. doi: 10.1073/pnas.81.10.3185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Francoeur A. M., Mathews M. B. Interaction between VA RNA and the lupus antigen La: formation of a ribonucleoprotein particle in vitro. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6772–6776. doi: 10.1073/pnas.79.22.6772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Giallongo A., Kochoumian L., King T. P. Enzyme and radioimmunoassays for specific murine IgE and IgG with different solid-phase immunosorbents. J Immunol Methods. 1982 Aug 13;52(3):379–393. doi: 10.1016/0022-1759(82)90009-6. [DOI] [PubMed] [Google Scholar]
  7. Habets W. J., de Rooij D. J., Salden M. H., Verhagen A. P., van Eekelen C. A., van de Putte L. B., van Venrooij W. J. Antibodies against distinct nuclear matrix proteins are characteristic for mixed connective tissue disease. Clin Exp Immunol. 1983 Oct;54(1):265–276. [PMC free article] [PubMed] [Google Scholar]
  8. Hinterberger M., Pettersson I., Steitz J. A. Isolation of small nuclear ribonucleoproteins containing U1, U2, U4, U5, and U6 RNAs. J Biol Chem. 1983 Feb 25;258(4):2604–2613. [PubMed] [Google Scholar]
  9. Keiser H. D., Weinstein J. The detection and identification of antibodies to saline extractable nuclear antigens by counterimmunoelectrophoresis. Arthritis Rheum. 1980 Sep;23(9):1026–1035. doi: 10.1002/art.1780230910. [DOI] [PubMed] [Google Scholar]
  10. Kinlaw C. S., Robberson B. L., Berget S. M. Fractionation and characterization of human small nuclear ribonucleoproteins containing U1 and U2 RNAs. J Biol Chem. 1983 Jun 10;258(11):7181–7189. [PubMed] [Google Scholar]
  11. Kurata N., Tan E. M. Identification of antibodies to nuclear acidic antigens by counterimmunoelectrophoresis. Arthritis Rheum. 1976 May-Jun;19(3):574–580. doi: 10.1002/art.1780190309. [DOI] [PubMed] [Google Scholar]
  12. Lerner M. R., Andrews N. C., Miller G., Steitz J. A. Two small RNAs encoded by Epstein-Barr virus and complexed with protein are precipitated by antibodies from patients with systemic lupus erythematosus. Proc Natl Acad Sci U S A. 1981 Feb;78(2):805–809. doi: 10.1073/pnas.78.2.805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lerner M. R., Boyle J. A., Mount S. M., Wolin S. L., Steitz J. A. Are snRNPs involved in splicing? Nature. 1980 Jan 10;283(5743):220–224. doi: 10.1038/283220a0. [DOI] [PubMed] [Google Scholar]
  14. Lerner M. R., Steitz J. A. Antibodies to small nuclear RNAs complexed with proteins are produced by patients with systemic lupus erythematosus. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5495–5499. doi: 10.1073/pnas.76.11.5495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mathews M. B., Bernstein R. M. Myositis autoantibody inhibits histidyl-tRNA synthetase: a model for autoimmunity. Nature. 1983 Jul 14;304(5922):177–179. doi: 10.1038/304177a0. [DOI] [PubMed] [Google Scholar]
  16. Mattioli M., Reichlin M. Characterization of a soluble nuclear ribonucleoprotein antigen reactive with SLE sera. J Immunol. 1971 Nov;107(5):1281–1290. [PubMed] [Google Scholar]
  17. Mattioli M., Reichlin M. Physical association of two nuclear antigens and mutual occurrence of their antibodies: the relationship of the SM and RNAprotein (MO) systems in SLE sera. J Immunol. 1973 May;110(5):1318–1324. [PubMed] [Google Scholar]
  18. Mimori T., Hinterberger M., Pettersson I., Steitz J. A. Autoantibodies to the U2 small nuclear ribonucleoprotein in a patient with scleroderma-polymyositis overlap syndrome. J Biol Chem. 1984 Jan 10;259(1):560–565. [PubMed] [Google Scholar]
  19. Moore T. L., Weiss T. D., Neucks S. H., Baldassare A. R., Zuckner J. Extractable nuclear antigens. Semin Arthritis Rheum. 1981 May;10(4):309–318. doi: 10.1016/0049-0172(81)90007-x. [DOI] [PubMed] [Google Scholar]
  20. Okayasu I., Hatakeyama S. The difference of susceptibility of target thyroid gland to autoimmune thyroiditis induced by a combination of implantation of thyroid gland and injection of lipopolysaccharide. Clin Immunol Immunopathol. 1983 Oct;29(1):51–57. doi: 10.1016/0090-1229(83)90006-5. [DOI] [PubMed] [Google Scholar]
  21. Pettersson I., Hinterberger M., Mimori T., Gottlieb E., Steitz J. A. The structure of mammalian small nuclear ribonucleoproteins. Identification of multiple protein components reactive with anti-(U1)ribonucleoprotein and anti-Sm autoantibodies. J Biol Chem. 1984 May 10;259(9):5907–5914. [PubMed] [Google Scholar]
  22. Schur P. H., Meyer I., Garovoy M., Carpenter C. B. Associations between systemic lupus erythematosus and the major histocompatibility complex: clinical and immunological considerations. Clin Immunol Immunopathol. 1982 Aug;24(2):263–275. doi: 10.1016/0090-1229(82)90237-9. [DOI] [PubMed] [Google Scholar]
  23. Sharp G. C., Irvin W. S., May C. M., Holman H. R., McDuffie F. C., Hess E. V., Schmid F. R. Association of antibodies to ribonucleoprotein and Sm antigens with mixed connective-tissue disease, systematic lupus erythematosus and other rheumatic diseases. N Engl J Med. 1976 Nov 18;295(21):1149–1154. doi: 10.1056/NEJM197611182952101. [DOI] [PubMed] [Google Scholar]
  24. Sharp G. C., Irvin W. S., Tan E. M., Gould R. G., Holman H. R. Mixed connective tissue disease--an apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA). Am J Med. 1972 Feb;52(2):148–159. doi: 10.1016/0002-9343(72)90064-2. [DOI] [PubMed] [Google Scholar]
  25. Tan E. M. Autoantibodies to nuclear antigens (ANA): their immunobiology and medicine. Adv Immunol. 1982;33:167–240. doi: 10.1016/s0065-2776(08)60836-6. [DOI] [PubMed] [Google Scholar]
  26. Tan E. M., Cohen A. S., Fries J. F., Masi A. T., McShane D. J., Rothfield N. F., Schaller J. G., Talal N., Winchester R. J. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271–1277. doi: 10.1002/art.1780251101. [DOI] [PubMed] [Google Scholar]
  27. Weigle W. O. Self-nonself recognition by T and B lymphocytes and their roles in autoimmune phenomena. Arthritis Rheum. 1981 Aug;24(8):1044–1053. doi: 10.1002/art.1780240810. [DOI] [PubMed] [Google Scholar]
  28. White P. J., Billings P. B., Hoch S. O. Assays for the Sm and RNP autoantigens: the requirement for RNA and influence of the tissue source. J Immunol. 1982 Jun;128(6):2751–2756. [PubMed] [Google Scholar]
  29. White P. J., Gardner W. D., Hoch S. O. Identification of the immunogenically active components of the Sm and RNP antigens. Proc Natl Acad Sci U S A. 1981 Jan;78(1):626–630. doi: 10.1073/pnas.78.1.626. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. White P. J., Hoch S. O. Definition of the antigenic polypeptides in the Sm and RNP ribonucleoprotein complexes. Biochem Biophys Res Commun. 1981 Sep 16;102(1):365–371. doi: 10.1016/0006-291x(81)91530-8. [DOI] [PubMed] [Google Scholar]
  31. Williamson G. G., Pennebaker J., Boyle J. A. Clinical characteristics of patients with rheumatic disorders who possess antibodies against ribonucleoprotein particles. Arthritis Rheum. 1983 Apr;26(4):509–515. doi: 10.1002/art.1780260409. [DOI] [PubMed] [Google Scholar]
  32. Yang V. W., Lerner M. R., Steitz J. A., Flint S. J. A small nuclear ribonucleoprotein is required for splicing of adenoviral early RNA sequences. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1371–1375. doi: 10.1073/pnas.78.3.1371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Yankner B. A., Shooter E. M. Nerve growth factor in the nucleus: interaction with receptors on the nuclear membrane. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1269–1273. doi: 10.1073/pnas.76.3.1269. [DOI] [PMC free article] [PubMed] [Google Scholar]

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