Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1982 Jul;70(1):141–147. doi: 10.1172/JCI110587

Antibodies from patients with connective tissue diseases bind specific subsets of cellular RNA-protein particles.

J A Hardin, D R Rahn, C Shen, M R Lerner, S L Wolin, M D Rosa, J A Steitz
PMCID: PMC370236  PMID: 6806318

Abstract

We characterized the RNA-containing antigens precipitated by sera from 260 patients with positive antinuclear antibodies. 49 individuals, most of whom had systemic lupus erythematosus or Sjögren's syndrome, possessed antibodies that precipitated the previously identified RNP, Sm, Ro, and La antigens either singly or in combinations. These antigens, which are located on discrete sets of small nuclear or cytoplasmic RNA-protein particles, exhibited a number of antigenic interrelationships. One patient's serum recognized a new particle containing a small RNA which we have called Th; it also precipitated the Ro complexes. Other patients with systemic lupus erythematosus, hepatitis B virus infection, juvenile rheumatoid arthritis, myositis, and rheumatoid arthritis had antibodies that precipitated specific subsets of ribosomal RNA and transfer RNA. One patient's serum contained a monoclonal immunoglobulin G that precipitated ribosomes. Most of these antibodies identified antigenic determinants constituted at least in part of protein. The specificity of the proteins bound to particular cellular RNA, probably explains the exquisite precision with which antibodies from rheumatic disease patients discriminate among RNA subsets. Such sera should be useful probes for investigating specific roles that different RNA and RNA-protein complexes play in cellular metabolism.

Full text

PDF
141

Images in this article

142Image
on p.142

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akizuki M., Powers R., Holman H. R. A soluble acidic protein of the cell nucleus which reacts with serum from patients with systemic lupus erythermatosus and Sjögren's syndrome. J Clin Invest. 1977 Feb;59(2):264–272. doi: 10.1172/JCI108637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alspaugh M. A., Tan E. M. Antibodies to cellular antigens in Sjögren's syndrome. J Clin Invest. 1975 May;55(5):1067–1073. doi: 10.1172/JCI108007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Alspaugh M., Maddison P. Resolution of the identity of certain antigen-antibody systems in systemic lupus erythematosus and Sjögren's syndrome: an interlaboratory collaboration. Arthritis Rheum. 1979 Jul;22(7):796–798. doi: 10.1002/art.1780220719. [DOI] [PubMed] [Google Scholar]
  4. Clark G., Reichlin M., Tomasi T. B., Jr Characterization of a soluble cytoplasmic antigen reactive with sera from patients with systemic lupus erythmatosus. J Immunol. 1969 Jan;102(1):117–122. [PubMed] [Google Scholar]
  5. Eilat D., Steinberg A. D., Schechter A. N. The reaction of SLE antibodies with native, single stranded RNA: radioassay and binding specificities. J Immunol. 1978 Feb;120(2):550–557. [PubMed] [Google Scholar]
  6. Hamilton T. C., Smith A. G., Griffin C. A., Henderson R. J., Jr Ribonucleic acid in plasma from normal adults and multiple myeloma patients. Clin Chem. 1979 Oct;25(10):1774–1779. [PubMed] [Google Scholar]
  7. Hendrick J. P., Wolin S. L., Rinke J., Lerner M. R., Steitz J. A. Ro small cytoplasmic ribonucleoproteins are a subclass of La ribonucleoproteins: further characterization of the Ro and La small ribonucleoproteins from uninfected mammalian cells. Mol Cell Biol. 1981 Dec;1(12):1138–1149. doi: 10.1128/mcb.1.12.1138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Holman H. R. Partial purification and characterization of an extractible nuclear antigen which reacts with SLE sera. Ann N Y Acad Sci. 1965 Jun 30;124(2):800–806. doi: 10.1111/j.1749-6632.1965.tb19002.x. [DOI] [PubMed] [Google Scholar]
  9. Lerner M. R., Boyle J. A., Hardin J. A., Steitz J. A. Two novel classes of small ribonucleoproteins detected by antibodies associated with lupus erythematosus. Science. 1981 Jan 23;211(4480):400–402. doi: 10.1126/science.6164096. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. Mattioli M., Reichlin M. Heterogeneity of RNA protein antigens reactive with sera of patients with systemic lupus erythematosus. Description of a cytoplasmic nonribosomal antigen. Arthritis Rheum. 1974 Jul-Aug;17(4):421–429. doi: 10.1002/art.1780170413. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. ROPES M. W., BENNETT G. A., COBB S., JACOX R., JESSAR R. A. 1958 Revision of diagnostic criteria for rheumatoid arthritis. Bull Rheum Dis. 1958 Dec;9(4):175–176. [PubMed] [Google Scholar]
  15. Rogers J., Wall R. A mechanism for RNA splicing. Proc Natl Acad Sci U S A. 1980 Apr;77(4):1877–1879. doi: 10.1073/pnas.77.4.1877. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Schur P. H., Monroe M. Antibodies to ribonucleic acid in systemic lupus erythematosus. Proc Natl Acad Sci U S A. 1969 Aug;63(4):1108–1112. doi: 10.1073/pnas.63.4.1108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Steinman C. R. Free DNA in serum and plasma from normal adults. J Clin Invest. 1975 Aug;56(2):512–515. doi: 10.1172/JCI108118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Tan E. M., Kunkel H. G. Characteristics of a soluble nuclear antigen precipitating with sera of patients with systemic lupus erythematosus. J Immunol. 1966 Mar;96(3):464–471. [PubMed] [Google Scholar]
  20. Tan E. M. Relationship of nuclear staining patterns with precipitating antibodies in systemic lupus erythematosus. J Lab Clin Med. 1967 Nov;70(5):800–812. [PubMed] [Google Scholar]
  21. WIEME R. J. An improved technique of agar-gel electrophoresis on microscope slides. Clin Chim Acta. 1959 May;4(3):317–321. doi: 10.1016/0009-8981(59)90096-8. [DOI] [PubMed] [Google Scholar]
  22. 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]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES