Skip to main content
PMC home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1993 Apr;92(1):51–57. doi: 10.1111/j.1365-2249.1993.tb05947.x

Interactions of anti-DNA antibodies with Z-DNA.

P Krishna 1, M J Fritzler 1, J H Van de Sande 1
PMCID: PMC1554883  PMID: 8467564

Abstract

Systemic lupus erythematosus (SLE) sera, two classes of serum lipoproteins, and IgG antibodies from SLE and normal sera were tested for their reactivity with a Z-DNA polymer, Br-poly (dG-dC). In all cases preferential binding to Z-DNA over B-DNA was observed. This interaction, for the most part, could be inhibited by the negatively charged phospholipid, cardiolipin, which suggests that most of the anti-Z-DNA activity associated with sera arises from relatively non-specific ionic interactions between proteins and polyanionic molecules. An assay has been described that can eliminate proteins cross-reactive with negatively charged phospholipids.

Full text

PDF
55

Images in this article

54Fig. 2
on p.54
55Fig. 4
on p.55
56Fig. 5
on p.56

Selected References

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

  1. Bergen H. R., 3rd, Losman M. J., O'Connor T., Zacharias W., Larson J. E., Accavitti M. A., Wells R. D., Koopman W. J. Specificity of monoclonal anti-Z-DNA antibodies from unimmunized MRL/Mp-lpr/lpr mice. J Immunol. 1987 Aug 1;139(3):743–748. [PubMed] [Google Scholar]
  2. Bowen B., Steinberg J., Laemmli U. K., Weintraub H. The detection of DNA-binding proteins by protein blotting. Nucleic Acids Res. 1980 Jan 11;8(1):1–20. doi: 10.1093/nar/8.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brinkman K., Termaat R., Berden J. H., Smeenk R. J. Anti-DNA antibodies and lupus nephritis: the complexity of crossreactivity. Immunol Today. 1990 Jul;11(7):232–234. doi: 10.1016/0167-5699(90)90095-q. [DOI] [PubMed] [Google Scholar]
  4. Fisher W. R., Schumaker V. N. Isolation and characterization of apolipoprotein B-100. Methods Enzymol. 1986;128:247–262. doi: 10.1016/0076-6879(86)28071-4. [DOI] [PubMed] [Google Scholar]
  5. Galli M., Comfurius P., Maassen C., Hemker H. C., de Baets M. H., van Breda-Vriesman P. J., Barbui T., Zwaal R. F., Bevers E. M. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet. 1990 Jun 30;335(8705):1544–1547. doi: 10.1016/0140-6736(90)91374-j. [DOI] [PubMed] [Google Scholar]
  6. Galli M., Cortelazzo S., Daldossi M., Barbui T. Increased levels of beta 2-glycoprotein I (aca-Cofactor) in patients with lupus anticoagulant. Thromb Haemost. 1992 Mar 2;67(3):386–386. [PubMed] [Google Scholar]
  7. Ginsberg B., Keiser H. A Millipore filter assay for antibodies to native DNA in sera of patients with systemic lupus erythematosus. Arthritis Rheum. 1973 Mar-Apr;16(2):199–207. doi: 10.1002/art.1780160210. [DOI] [PubMed] [Google Scholar]
  8. Harris E. N., Gharavi A. E., Hughes G. R. Anti-phospholipid antibodies. Clin Rheum Dis. 1985 Dec;11(3):591–609. [PubMed] [Google Scholar]
  9. Ichikawa Y., Takamatsu K., Shimizu H., Uchiyama M., Moriuchi J., Takaya M., Kobayashi N., Kawada T., Arimori S. Serum apolipoprotein H levels in systemic lupus erythematosus are not influenced by antiphospholipid antibodies. Lupus. 1992 May;1(3):145–149. doi: 10.1177/096120339200100305. [DOI] [PubMed] [Google Scholar]
  10. Krippner H., Boehm B. O., Pirlet K. Antibodies to dsDNA: failure to detect antigenic determinants specific for superhelical B-DNA. Mol Immunol. 1985 Jun;22(6):623–627. doi: 10.1016/0161-5890(85)90091-4. [DOI] [PubMed] [Google Scholar]
  11. Krishna P., Kennedy B. P., Waisman D. M., van de Sande J. H., McGhee J. D. Are many Z-DNA binding proteins actually phospholipid-binding proteins? Proc Natl Acad Sci U S A. 1990 Feb;87(4):1292–1295. doi: 10.1073/pnas.87.4.1292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Krishna P., Kennedy B. P., van de Sande J. H., McGhee J. D. Yolk proteins from nematodes, chickens, and frogs bind strongly and preferentially to left-handed Z-DNA. J Biol Chem. 1988 Dec 15;263(35):19066–19070. [PubMed] [Google Scholar]
  13. Krishna P., Morgan A. R., van de Sande J. H. Interaction of recA protein with left-handed Z-DNA. Biochem J. 1991 May 1;275(Pt 3):711–719. doi: 10.1042/bj2750711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Krishna P., van de Sande J. H. Interaction of RecA protein with acidic phospholipids inhibits DNA-binding activity of RecA. J Bacteriol. 1990 Nov;172(11):6452–6458. doi: 10.1128/jb.172.11.6452-6458.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kumar V., Krasny S., Beutner E. H. Specificity of the Crithidia luciliae method for detecting anti-DNA antibodies. Effect of absorption for lipoproteins. Immunol Invest. 1985 Jun;14(3):199–210. doi: 10.3109/08820138509076144. [DOI] [PubMed] [Google Scholar]
  16. Lafer E. M., Möller A., Nordheim A., Stollar B. D., Rich A. Antibodies specific for left-handed Z-DNA. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3546–3550. doi: 10.1073/pnas.78.6.3546. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lafer E. M., Rauch J., Andrzejewski C., Jr, Mudd D., Furie B., Furie B., Schwartz R. S., Stollar B. D. Polyspecific monoclonal lupus autoantibodies reactive with both polynucleotides and phospholipids. J Exp Med. 1981 Apr 1;153(4):897–909. doi: 10.1084/jem.153.4.897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lafer E. M., Valle R. P., Möller A., Nordheim A., Schur P. H., Rich A., Stollar B. D. Z-DNA-specific antibodies in human systemic lupus erythematosus. J Clin Invest. 1983 Feb;71(2):314–321. doi: 10.1172/JCI110771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lee J. S., Woodsworth M. L., Latimer L. J. Functional groups on 'Z' DNA recognized by monoclonal antibodies. FEBS Lett. 1984 Mar 26;168(2):303–306. doi: 10.1016/0014-5793(84)80267-7. [DOI] [PubMed] [Google Scholar]
  20. McNeil H. P., Simpson R. J., Chesterman C. N., Krilis S. A. Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: beta 2-glycoprotein I (apolipoprotein H). Proc Natl Acad Sci U S A. 1990 Jun;87(11):4120–4124. doi: 10.1073/pnas.87.11.4120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nimpf J., Wurm H., Kostner G. M. Interaction of beta 2-glycoprotein-I with human blood platelets: influence upon the ADP-induced aggregation. Thromb Haemost. 1985 Aug 30;54(2):397–401. [PubMed] [Google Scholar]
  22. Oosting J. D., Derksen R. H., Entjes H. T., Bouma B. N., de Groot P. G. Lupus anticoagulant activity is frequently dependent on the presence of beta 2-glycoprotein I. Thromb Haemost. 1992 May 4;67(5):499–502. [PubMed] [Google Scholar]
  23. Petri M. The clinical syndrome associated with antiphospholipid antibodies. J Rheumatol. 1992 Apr;19(4):505–507. [PubMed] [Google Scholar]
  24. Rohner K. J., Hobi R., Kuenzle C. C. Z-DNA-binding proteins. Identification critically depends on the proper choice of ligands. J Biol Chem. 1990 Nov 5;265(31):19112–19115. [PubMed] [Google Scholar]
  25. Sibley J. T., Lee J. S., Decoteau W. E. Left-handed "Z" DNA antibodies in rheumatoid arthritis and systemic lupus erythematosus. J Rheumatol. 1984 Oct;11(5):633–637. [PubMed] [Google Scholar]
  26. Sinha A. A., Lopez M. T., McDevitt H. O. Autoimmune diseases: the failure of self tolerance. Science. 1990 Jun 15;248(4961):1380–1388. doi: 10.1126/science.1972595. [DOI] [PubMed] [Google Scholar]
  27. Stollar B. D. Antibodies to DNA. CRC Crit Rev Biochem. 1986;20(1):1–36. doi: 10.3109/10409238609115899. [DOI] [PubMed] [Google Scholar]
  28. Tan E. M. Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology. Adv Immunol. 1989;44:93–151. doi: 10.1016/s0065-2776(08)60641-0. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Thomas T. J., Meryhew N. L., Messner R. P. DNA sequence and conformation specificity of lupus autoantibodies. Preferential binding to the left-handed Z-DNA form of synthetic polynucleotides. Arthritis Rheum. 1988 Mar;31(3):367–377. doi: 10.1002/art.1780310308. [DOI] [PubMed] [Google Scholar]
  31. Thomas T. J., Meryhew N. L., Messner R. P. Enhanced binding of lupus sera to the polyamine-induced left-handed Z-DNA form of polynucleotides. Arthritis Rheum. 1990 Mar;33(3):356–365. doi: 10.1002/art.1780330308. [DOI] [PubMed] [Google Scholar]
  32. Van Helden P. D., Van Lill L., Bester A. J., De Waal L., Hoal-van Helden E. G. A new assay for anti-DNA antibodies in serum which includes the measurement of anti-Z-DNA. Clin Exp Immunol. 1987 Aug;69(2):394–402. [PMC free article] [PubMed] [Google Scholar]
  33. Zouali M., Migliorini P., Stollar D. B. Murine lupus anti-DNA antibodies cross-react with the hapten (4-hydroxy-5-iodo-3-nitrophenyl)acetyl, but immunization-induced anti-DNA antibodies do not. Eur J Immunol. 1987 Apr;17(4):509–513. doi: 10.1002/eji.1830170412. [DOI] [PubMed] [Google Scholar]
  34. van Helden P. D., Bester A. J. Naturally occurring anti-DNA antibodies from systemic lupus erythematosus patients may be used to study gene expression in vitro. Biochim Biophys Acta. 1988 Mar 31;949(3):273–278. doi: 10.1016/0167-4781(88)90152-2. [DOI] [PubMed] [Google Scholar]
  35. van de Sande J. H., Jovin T. M. Z* DNA, the left-handed helical form of poly[d(G-C)] in MgCl2-ethanol, is biologically active. EMBO J. 1982;1(1):115–120. doi: 10.1002/j.1460-2075.1982.tb01133.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES