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. 2003 May;62(5):431–434. doi: 10.1136/ard.62.5.431

Anti-chromatin antibodies in systemic lupus erythematosus: a useful marker for lupus nephropathy

R Cervera 1, O Vinas 1, M Ramos-Casals 1, J Font 1, M Garcia-Carrasco 1, A Siso 1, F Ramirez 1, Y Machuca 1, J Vives 1, M Ingelmo 1, R Burlingame 1
PMCID: PMC1754546  PMID: 12695155

Abstract

Background: Anti-chromatin antibodies have recently been described in patients with systemic lupus erythematosus (SLE) and it has been suggested that their presence is associated with lupus nephritis.

Objective: To assess the prevalence and clinical associations of these antibodies in SLE.

Methods: The presence of anti-chromatin antibodies in 100 patients with SLE was investigated by an enzyme linked immunosorbent assay (ELISA). To determine the specificity of these antibodies, 100 patients with primary Sjögren's syndrome, 30 with primary antiphospholipid syndrome (APS), 10 with systemic sclerosis, and 100 normal controls were also tested.

Results: Positive levels were detected in 69/100 (69%) patients with SLE. In contrast, they were found in only 8/100 (8%) of those with primary Sjögren's syndrome, in 1/10 (10%) with systemic sclerosis, in 2/30 (7%) with primary APS, and in none of the 100 healthy controls. Patients with anti-chromatin antibodies had a twofold higher prevalence of lupus nephropathy than those without these antibodies (58% v 29%, p<0.01). A significant correlation was found between the levels of anti-chromatin antibodies and disease activity score as measured by the European Consensus Lupus Activity Measurement (ECLAM; p=0.011).

Conclusions: The measurement of anti-chromatin antibodies appears to be a useful addition to the laboratory tests that can help in the diagnosis and treatment of SLE. These antibodies are both sensitive and specific for SLE, and are a useful marker for an increased risk of lupus nephritis.

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Figure 1.

Figure 1

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Correlation between the levels of anti-chromatin antibodies and SLE disease activity score as measured by ECLAM.

Figure 2.

Figure 2

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Correlation between the levels of anti-chromatin antibodies and those of anti-dsDNA antibodies.

Figure 3.

Figure 3

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Serial determinations of both anti-chromatin and anti-dsDNA antibodies in a patient who developed lupus nephropathy during the study period, showing that anti-chromatin antibodies appeared before anti-dsDNA antibodies.

Selected References

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

  1. Amoura Z., Koutouzov S., Chabre H., Cacoub P., Amoura I., Musset L., Bach J. F., Piette J. C. Presence of antinucleosome autoantibodies in a restricted set of connective tissue diseases: antinucleosome antibodies of the IgG3 subclass are markers of renal pathogenicity in systemic lupus erythematosus. Arthritis Rheum. 2000 Jan;43(1):76–84. doi: 10.1002/1529-0131(200001)43:1<76::AID-ANR10>3.0.CO;2-I. [DOI] [PubMed] [Google Scholar]
  2. Amoura Z., Piette J. C., Bach J. F., Koutouzov S. The key role of nucleosomes in lupus. Arthritis Rheum. 1999 May;42(5):833–843. doi: 10.1002/1529-0131(199905)42:5<833::AID-ANR1>3.0.CO;2-T. [DOI] [PubMed] [Google Scholar]
  3. Askanase A. D., Friedman D. M., Copel J., Dische M. R., Dubin A., Starc T. J., Katholi M. C., Buyon J. P. Spectrum and progression of conduction abnormalities in infants born to mothers with anti-SSA/Ro-SSB/La antibodies. Lupus. 2002;11(3):145–151. doi: 10.1191/0961203302lu173oa. [DOI] [PubMed] [Google Scholar]
  4. Bruns A., Bläss S., Hausdorf G., Burmester G. R., Hiepe F. Nucleosomes are major T and B cell autoantigens in systemic lupus erythematosus. Arthritis Rheum. 2000 Oct;43(10):2307–2315. doi: 10.1002/1529-0131(200010)43:10<2307::AID-ANR19>3.0.CO;2-J. [DOI] [PubMed] [Google Scholar]
  5. Burlingame R. W., Boey M. L., Starkebaum G., Rubin R. L. The central role of chromatin in autoimmune responses to histones and DNA in systemic lupus erythematosus. J Clin Invest. 1994 Jul;94(1):184–192. doi: 10.1172/JCI117305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Burlingame R. W., Rubin R. L., Balderas R. S., Theofilopoulos A. N. Genesis and evolution of antichromatin autoantibodies in murine lupus implicates T-dependent immunization with self antigen. J Clin Invest. 1993 Apr;91(4):1687–1696. doi: 10.1172/JCI116378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cervera R., Font J., López-Soto A., Casals F., Pallarés L., Bové A., Ingelmo M., Urbano-Márquez A. Isotype distribution of anticardiolipin antibodies in systemic lupus erythematosus: prospective analysis of a series of 100 patients. Ann Rheum Dis. 1990 Feb;49(2):109–113. doi: 10.1136/ard.49.2.109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cervera R., Khamashta M. A., Font J., Sebastiani G. D., Gil A., Lavilla P., Aydintug A. O., Jedryka-Góral A., de Ramón E., Fernández-Nebro A. Morbidity and mortality in systemic lupus erythematosus during a 5-year period. A multicenter prospective study of 1,000 patients. European Working Party on Systemic Lupus Erythematosus. Medicine (Baltimore) 1999 May;78(3):167–175. doi: 10.1097/00005792-199905000-00003. [DOI] [PubMed] [Google Scholar]
  9. Cervera R., Khamashta M. A., Font J., Sebastiani G. D., Gil A., Lavilla P., Doménech I., Aydintug A. O., Jedryka-Góral A., de Ramón E. Systemic lupus erythematosus: clinical and immunologic patterns of disease expression in a cohort of 1,000 patients. The European Working Party on Systemic Lupus Erythematosus. Medicine (Baltimore) 1993 Mar;72(2):113–124. [PubMed] [Google Scholar]
  10. Exner T., Triplett D. A., Taberner D., Machin S. J. Guidelines for testing and revised criteria for lupus anticoagulants. SSC Subcommittee for the Standardization of Lupus Anticoagulants. Thromb Haemost. 1991 Mar 4;65(3):320–322. [PubMed] [Google Scholar]
  11. Gharavi A. E., Harris E. N., Asherson R. A., Hughes G. R. Anticardiolipin antibodies: isotype distribution and phospholipid specificity. Ann Rheum Dis. 1987 Jan;46(1):1–6. doi: 10.1136/ard.46.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Grishman E., Gerber M. A., Churg J. Patterns of renal injury in systemic lupus erythematosus: light and immunofluorescence microscopic observations. Am J Kidney Dis. 1982 Jul;2(1 Suppl 1):135–141. [PubMed] [Google Scholar]
  13. Hmida YoussefBenHadj, Schmit Patrick, Gilson Georges, Humbel René-Louis. Failure to detect antinucleosome antibodies in scleroderma: comment on the article by Amoura et al. Arthritis Rheum. 2002 Jan;46(1):280–282. doi: 10.1002/1529-0131(200201)46:1<280::AID-ART10079>3.0.CO;2-A. [DOI] [PubMed] [Google Scholar]
  14. Kramers C., Hylkema M. N., van Bruggen M. C., van de Lagemaat R., Dijkman H. B., Assmann K. J., Smeenk R. J., Berden J. H. Anti-nucleosome antibodies complexed to nucleosomal antigens show anti-DNA reactivity and bind to rat glomerular basement membrane in vivo. J Clin Invest. 1994 Aug;94(2):568–577. doi: 10.1172/JCI117371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Morel L., Blenman K. R., Croker B. P., Wakeland E. K. The major murine systemic lupus erythematosus susceptibility locus, Sle1, is a cluster of functionally related genes. Proc Natl Acad Sci U S A. 2001 Jan 23;98(4):1787–1792. doi: 10.1073/pnas.031336098. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rosner S., Ginzler E. M., Diamond H. S., Weiner M., Schlesinger M., Fries J. F., Wasner C., Medsger T. A., Jr, Ziegler G., Klippel J. H. A multicenter study of outcome in systemic lupus erythematosus. II. Causes of death. Arthritis Rheum. 1982 Jun;25(6):612–617. doi: 10.1002/art.1780250602. [DOI] [PubMed] [Google Scholar]
  18. Schett G., Rubin R. L., Steiner G., Hiesberger H., Muller S., Smolen J. The lupus erythematosus cell phenomenon: comparative analysis of antichromatin antibody specificity in lupus erythematosus cell-positive and -negative sera. Arthritis Rheum. 2000 Feb;43(2):420–428. doi: 10.1002/1529-0131(200002)43:2<420::AID-ANR24>3.0.CO;2-Z. [DOI] [PubMed] [Google Scholar]
  19. Steinberg A. D., Steinberg S. C. Long-term preservation of renal function in patients with lupus nephritis receiving treatment that includes cyclophosphamide versus those treated with prednisone only. Arthritis Rheum. 1991 Aug;34(8):945–950. doi: 10.1002/art.1780340803. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. 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]
  23. Van Venrooij W. J., Sillekens P. T. Small nuclear RNA associated proteins: autoantigens in connective tissue diseases. Clin Exp Rheumatol. 1989 Nov-Dec;7(6):635–645. [PubMed] [Google Scholar]
  24. Vitali C., Bencivelli W., Isenberg D. A., Smolen J. S., Snaith M. L., Sciuto M., d'Ascanio A., Bombardieri S. Disease activity in systemic lupus erythematosus: report of the Consensus Study Group of the European Workshop for Rheumatology Research. I. A descriptive analysis of 704 European lupus patients. European Consensus Study Group for Disease Activity in SLE. Clin Exp Rheumatol. 1992 Sep-Oct;10(5):527–539. [PubMed] [Google Scholar]
  25. Vitali C., Bombardieri S., Moutsopoulos H. M., Balestrieri G., Bencivelli W., Bernstein R. M., Bjerrum K. B., Braga S., Coll J., de Vita S. Preliminary criteria for the classification of Sjögren's syndrome. Results of a prospective concerted action supported by the European Community. Arthritis Rheum. 1993 Mar;36(3):340–347. doi: 10.1002/art.1780360309. [DOI] [PubMed] [Google Scholar]
  26. Wallace D. J., Lin H. C., Shen G. Q., Peter J. B. Antibodies to histone (H2A-H2B)-DNA complexes in the absence of antibodies to double-stranded DNA or to (H2A-H2B) complexes are more sensitive and specific for scleroderma-related disorders than for lupus. Arthritis Rheum. 1994 Dec;37(12):1795–1797. doi: 10.1002/art.1780371213. [DOI] [PubMed] [Google Scholar]
  27. Wilson W. A., Gharavi A. E., Koike T., Lockshin M. D., Branch D. W., Piette J. C., Brey R., Derksen R., Harris E. N., Hughes G. R. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum. 1999 Jul;42(7):1309–1311. doi: 10.1002/1529-0131(199907)42:7<1309::AID-ANR1>3.0.CO;2-F. [DOI] [PubMed] [Google Scholar]

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