Abstract
A simple, rapid assay for measuring anti-DNA titre of serum which includes anti-Z-DNA is described. The assay involves solution binding of antibody to labelled DNA under conditions such that the DNA is altered to form a left-handed or Z-DNA structure in the presence of cobalt ions. The absence or presence of cobalt determines a B or Z form structure in DNA and antibodies to these forms are detectable. The majority of SLE and RA patients (88%) have a higher anti-DNA titre in the presence of cobalt ions. An additional 25% of SLE patients and 22/23 RA patients who had normal anti-DNA levels according to the Crithidea assay, reacted with abnormal titres in our assay. Patients experiencing a relapse in SLE also showed a large increase in anti-DNA in the presence of antigenic Z-DNA. These results suggest that monitoring anti-DNA levels in SLE and RA to detect anti-Z DNA antibodies, provides significant advantages over methods currently in use to measure anti-DNA antibodies.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Behe M., Felsenfeld G. Effects of methylation on a synthetic polynucleotide: the B--Z transition in poly(dG-m5dC).poly(dG-m5dC). Proc Natl Acad Sci U S A. 1981 Mar;78(3):1619–1623. doi: 10.1073/pnas.78.3.1619. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berne B. H., Galland K. T., Welton R. C. Values of the U.S. National Reference Serum for human antibodies to native DNA obtained with commercial immunoassays for anti-DNA in systemic lupus erythematosus. Clin Chem. 1984 May;30(5):757–759. [PubMed] [Google Scholar]
- CASALS S. P., FRIOU G. J., MYERS L. L. SIGNIFICANCE OF ANTIBODY TO DNA IN SYSTEMIC LUPUS ERYTHEMATOSUS. Arthritis Rheum. 1964 Aug;7:379–390. doi: 10.1002/art.1780070404. [DOI] [PubMed] [Google Scholar]
- Casperson G. F., Voss E. W., Jr Colicin E1 plasmid as a probe for detection and study of anti-dna activity in SLE sera. J Immunol Methods. 1980;36(3-4):293–308. doi: 10.1016/0022-1759(80)90134-9. [DOI] [PubMed] [Google Scholar]
- Gessner R. V., Quigley G. J., Wang A. H., van der Marel G. A., van Boom J. H., Rich A. Structural basis for stabilization of Z-DNA by cobalt hexaammine and magnesium cations. Biochemistry. 1985 Jan 15;24(2):237–240. doi: 10.1021/bi00323a001. [DOI] [PubMed] [Google Scholar]
- Koffler D., Carr R., Agnello V., Thoburn R., Kunkel H. G. Antibodies to polynucleotides in human sera: antigenic specificity and relation to disease. J Exp Med. 1971 Jul 1;134(1):294–312. doi: 10.1084/jem.134.1.294. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Möller A., Nordheim A., Kozlowski S. A., Patel D. J., Rich A. Bromination stabilizes poly(dG-dC) in the Z-DNA form under low-salt conditions. Biochemistry. 1984 Jan 3;23(1):54–62. doi: 10.1021/bi00296a009. [DOI] [PubMed] [Google Scholar]
- Peck L. J., Nordheim A., Rich A., Wang J. C. Flipping of cloned d(pCpG)n.d(pCpG)n DNA sequences from right- to left-handed helical structure by salt, Co(III), or negative supercoiling. Proc Natl Acad Sci U S A. 1982 Aug;79(15):4560–4564. doi: 10.1073/pnas.79.15.4560. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pennebaker J. B., Gilliam J. N., Ziff M. Immunoglobulin classes of DNA binding activity in serum and skin in systemic lupus erythematosus. J Clin Invest. 1977 Dec;60(6):1331–1338. doi: 10.1172/JCI108892. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pohl F. M., Jovin T. M. Salt-induced co-operative conformational change of a synthetic DNA: equilibrium and kinetic studies with poly (dG-dC). J Mol Biol. 1972 Jun 28;67(3):375–396. doi: 10.1016/0022-2836(72)90457-3. [DOI] [PubMed] [Google Scholar]
- Sano H., Morimoto C. Dna isolated from DNA/anti-DNA antibody immune complexes in systemic lupus erythematosus is rich in guanine-cytosine content. J Immunol. 1982 Mar;128(3):1341–1345. [PubMed] [Google Scholar]
- 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]
- 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]
- Van Helden P. D. Potential Z-DNA-forming elements in serum DNA from human systemic lupus erythematosus. J Immunol. 1985 Jan;134(1):177–179. [PubMed] [Google Scholar]
- Van Helden P. D. The effect of adriamycin on Z-DNA formation and DNA synthesis. Nucleic Acids Res. 1983 Dec 10;11(23):8415–8420. doi: 10.1093/nar/11.23.8415. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Winfield J. B., Koffler D., Kunkel H. G. Role of DNA-anti-DNA complexes in the immunopathogenesis of tissue injury in systemic lupus erythematosus. Scand J Rheumatol Suppl. 1975;11:59–64. doi: 10.3109/03009747509095630. [DOI] [PubMed] [Google Scholar]
- Zacharias W., Larson J. E., Klysik J., Stirdivant S. M., Wells R. D. Conditions which cause the right-handed to left-handed DNA conformational transitions. Evidence for several types of left-handed DNA structures in solution. J Biol Chem. 1982 Mar 25;257(6):2775–2782. [PubMed] [Google Scholar]
- Zarling D. A., Arndt-Jovin D. J., Robert-Nicoud M., McIntosh L. P., Thomae R., Jovin T. M. Immunoglobulin recognition of synthetic and natural left-handed Z DNA conformations and sequences. J Mol Biol. 1984 Jul 5;176(3):369–415. doi: 10.1016/0022-2836(84)90495-9. [DOI] [PubMed] [Google Scholar]