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. 1994 Jan;93(1):443–449. doi: 10.1172/JCI116980

Lupus autoantibodies to native DNA cross-react with the A and D SnRNP polypeptides.

M Reichlin 1, A Martin 1, E Taylor-Albert 1, K Tsuzaka 1, W Zhang 1, M W Reichlin 1, E Koren 1, F M Ebling 1, B Tsao 1, B H Hahn 1
PMCID: PMC293809  PMID: 8282818

Abstract

Antibodies to native DNA (nDNA) in sera from patients with systemic lupus erythematosus have been found to frequently correlate with antibodies to the A and D SnRNP proteins measured in Western blot assays. 40 of 54 SLE (74.1%) sera with anti-nDNA bound to A and D proteins, while 9 of 113 sera (8%) without anti-nDNA bound the A and D proteins, P < 10(-8) by Fisher's exact test. Antibodies to nDNA correlated closely with anti-A and anti-D in seven of eight patients followed sequentially, r = 0.7865. Nine human polyclonal anti-nDNA populations were isolated from DNA cellulose columns. Seven reacted equally with A and D, and two reacted predominantly with D. Two of three murine monoclonal anti-DNA antibodies isolated from NZB/NZW F1 hybrid mice bound A and D equally in Western blot with a titer > 1/40,000. These reactions were directed to the unfolded A and D proteins measurable in Western blot since these monoclonals (and several of the human anti-nDNA populations) failed to react with native U1RNP in ELISA or in RNA immunoprecipitation experiments. These newly recognized cross reactions of anti-nDNA may amplify the immune response to DNA and be part of the original immunogenic drive.

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Selected References

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

  1. Aarden L. A., de Groot E. R., Feltkamp T. E. Immunology of DNA. III. Crithidia luciliae, a simple substrate for the determination of anti-dsDNA with the immunofluorescence technique. Ann N Y Acad Sci. 1975 Jun 30;254:505–515. doi: 10.1111/j.1749-6632.1975.tb29197.x. [DOI] [PubMed] [Google Scholar]
  2. Bloom D. D., Davignon J. L., Cohen P. L., Eisenberg R. A., Clarke S. H. Overlap of the anti-Sm and anti-DNA responses of MRL/Mp-lpr/lpr mice. J Immunol. 1993 Feb 15;150(4):1579–1590. [PubMed] [Google Scholar]
  3. Bloom D. D., Davignon J. L., Retter M. W., Shlomchik M. J., Pisetsky D. S., Cohen P. L., Eisenberg R. A., Clarke S. H. V region gene analysis of anti-Sm hybridomas from MRL/Mp-lpr/lpr mice. J Immunol. 1993 Feb 15;150(4):1591–1610. [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. Diamond B., Scharff M. D. Somatic mutation of the T15 heavy chain gives rise to an antibody with autoantibody specificity. Proc Natl Acad Sci U S A. 1984 Sep;81(18):5841–5844. doi: 10.1073/pnas.81.18.5841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Forman M. S., Nakamura M., Mimori T., Gelpi C., Hardin J. A. Detection of antibodies to small nuclear ribonucleoproteins and small cytoplasmic ribonucleoproteins using unlabeled cell extracts. Arthritis Rheum. 1985 Dec;28(12):1356–1361. doi: 10.1002/art.1780281207. [DOI] [PubMed] [Google Scholar]
  7. Harley J. B., Sestak A. L., Willis L. G., Fu S. M., Hansen J. A., Reichlin M. A model for disease heterogeneity in systemic lupus erythematosus. Relationships between histocompatibility antigens, autoantibodies, and lymphopenia or renal disease. Arthritis Rheum. 1989 Jul;32(7):826–836. [PubMed] [Google Scholar]
  8. Hirakata M., Craft J., Hardin J. A. Autoantigenic epitopes of the B and D polypeptides of the U1 snRNP. Analysis of domains recognized by the Y12 monoclonal anti-Sm antibody and by patient sera. J Immunol. 1993 Apr 15;150(8 Pt 1):3592–3601. [PubMed] [Google Scholar]
  9. Itoh Y., Rader M. D., Reichlin M. Heterogeneity of the Ro/SSA antigen and autoanti-Ro/SSA response: evidence of the four antigenically distinct forms. Clin Exp Immunol. 1990 Jul;81(1):45–51. doi: 10.1111/j.1365-2249.1990.tb05289.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jacob L., Tron F., Bach J. F., Louvard D. A monoclonal anti-DNA antibody also binds to cell-surface protein(s). Proc Natl Acad Sci U S A. 1984 Jun;81(12):3843–3845. doi: 10.1073/pnas.81.12.3843. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Koffler D., Agnello V., Kimkel H. G. Polynucleotide immune complexes in serum and glomeruli of patients with systemic lupus erythematosus. Am J Pathol. 1974 Jan;74(1):109–124. [PMC free article] [PubMed] [Google Scholar]
  12. Koffler D., Agnello V., Thoburn R., Kunkel H. G. Systemic lupus erythematosus: prototype of immune complex nephritis in man. J Exp Med. 1971 Sep 1;134(3 Pt 2):169s–179s. [PubMed] [Google Scholar]
  13. Krishnan C., Kaplan M. H. Immunopathologic studies of systemic lupus erythematosus. II. Antinuclear reaction of gamma-globulin eluted from homogenates and isolated glomeruli of kidneys from patients with lupus nephritis. J Clin Invest. 1967 Apr;46(4):569–579. doi: 10.1172/JCI105558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Krishnan M. R., Marion T. N. Structural similarity of antibody variable regions from immune and autoimmune anti-DNA antibodies. J Immunol. 1993 Jun 1;150(11):4948–4957. [PubMed] [Google Scholar]
  15. Maddison P. J., Reichlin M. Deposition of antibodies to a soluble cytoplasmic antigen in the kidneys of patients with systemic lupus erythematosus. Arthritis Rheum. 1979 Aug;22(8):858–863. doi: 10.1002/art.1780220808. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Mendlovic S., Levy Y., Mozes E. Specific proliferative responses following the induction of experimental SLE in mice. Immunol Lett. 1991 Jan;27(1):69–73. doi: 10.1016/0165-2478(91)90247-8. [DOI] [PubMed] [Google Scholar]
  18. Mohan C., Adams S., Stanik V., Datta S. K. Nucleosome: a major immunogen for pathogenic autoantibody-inducing T cells of lupus. J Exp Med. 1993 May 1;177(5):1367–1381. doi: 10.1084/jem.177.5.1367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pisetsky D. S. Anti-DNA antibodies in systemic lupus erythematosus. Rheum Dis Clin North Am. 1992 May;18(2):437–454. [PubMed] [Google Scholar]
  20. Rajagopalan S., Zordan T., Tsokos G. C., Datta S. K. Pathogenic anti-DNA autoantibody-inducing T helper cell lines from patients with active lupus nephritis: isolation of CD4-8- T helper cell lines that express the gamma delta T-cell antigen receptor. Proc Natl Acad Sci U S A. 1990 Sep;87(18):7020–7024. doi: 10.1073/pnas.87.18.7020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Raz E., Ben-Bassat H., Davidi T., Shlomai Z., Eilat D. Cross-reactions of anti-DNA autoantibodies with cell surface proteins. Eur J Immunol. 1993 Feb;23(2):383–390. doi: 10.1002/eji.1830230213. [DOI] [PubMed] [Google Scholar]
  22. Rekvig O. P., Fredriksen K., Brannsether B., Moens U., Sundsfjord A., Traavik T. Antibodies to eukaryotic, including autologous, native DNA are produced during BK virus infection, but not after immunization with non-infectious BK DNA. Scand J Immunol. 1992 Sep;36(3):487–495. doi: 10.1111/j.1365-3083.1992.tb02964.x. [DOI] [PubMed] [Google Scholar]
  23. Schur P. H., Sandson J. Immunologic factors and clinical activity in systemic lupus erythematosus. N Engl J Med. 1968 Mar 7;278(10):533–538. doi: 10.1056/NEJM196803072781004. [DOI] [PubMed] [Google Scholar]
  24. Schwartz R. S., Stollar B. D. Origins of anti-DNA autoantibodies. J Clin Invest. 1985 Feb;75(2):321–327. doi: 10.1172/JCI111704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Tan E. M., Schur P. H., Carr R. I., Kunkel H. G. Deoxybonucleic acid (DNA) and antibodies to DNA in the serum of patients with systemic lupus erythematosus. J Clin Invest. 1966 Nov;45(11):1732–1740. doi: 10.1172/JCI105479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tsao B. P., Ebling F. M., Roman C., Panosian-Sahakian N., Calame K., Hahn B. H. Structural characteristics of the variable regions of immunoglobulin genes encoding a pathogenic autoantibody in murine lupus. J Clin Invest. 1990 Feb;85(2):530–540. doi: 10.1172/JCI114469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Vlahakos D., Foster M. H., Ucci A. A., Barrett K. J., Datta S. K., Madaio M. P. Murine monoclonal anti-DNA antibodies penetrate cells, bind to nuclei, and induce glomerular proliferation and proteinuria in vivo. J Am Soc Nephrol. 1992 Feb;2(8):1345–1354. doi: 10.1681/ASN.V281345. [DOI] [PubMed] [Google Scholar]
  29. Winfield J. B., Koffler D., Kunkel H. G. Specific concentration of polynucleotide immune complexes in the cryoprecipitates of patients with systemic lupus erythematosus. J Clin Invest. 1975 Sep;56(3):563–570. doi: 10.1172/JCI108125. [DOI] [PMC free article] [PubMed] [Google Scholar]

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