Relationship between anti-double-stranded DNA antibodies and exacerbation of renal disease in patients with systemic lupus erythematosus

Matthew D. Linnik, Jay Z. Hu, Kenneth R. Heilbrunn, Vibeke Strand, Frank L. Hurley, Tenshang Joh, D. Alarcón-Segovia, G. Appel, C. Aranow, S. Ballou, M. A. Becker, N. Becker, M. H. Belmont, A. Bohan, E. P. Boling, S. Bombardieri, W. G. Brelsford, J. P. Buyon, M. H. Cardiel, N. L. CarteronJ. J. Condemi, M. E. Cronin, J. J. Cush, R. DeHoratius, D. Desir, M. Edwards, M. A. El-Shahawy, P. Emery, L. R. Espinoza, T. H. Finkel, M. Fondal, P. Fortin, R. A. Furie, M. C. Genovese, T. Geppert, A. Gil-Aguado, G. S. Gilkeson, E. Ginzler, O. S. Gluck, J. L. Granda, J. Grossman, F. Hiepe, M. Hill, P. Howard, C. Hura, M. Ingelmo, A. Jaffer, J. Jakes, J. P. Kalden, K. C. Kalunian, G. M. Kammer, K. Kanick, J. Kaplan, S. Kaplan, R. Katz, H. M. Kenney, M. Khamashta, A. J. Kivitz, M. Krishnan, N. A. Kurtzman, M. Liebling, J. S. Lindberg, S. H. Lourie, J. Loveless, S. Manzi, K. Martin, J. McKay, J. Merrill, L. W. Moreland, M. C. Neuwelt, M. Petri, B. C. Poque, R. J. Quinet, R. Ramsey-Goldman, S. G. Rosenblatt, N. Rothfield, N. Scarpa, M. Schneider, J. T. Schousboe, L. K. Sewell, W. J. Shergy, Y. Sherrer, J. Sibilia, D. Smith, B. Spinowitz, M. Spira, R. Staud, S. Stern, M. P. Stevens, G. Sturfelt, W. Surbeck, E. A. Tindall, A. Torres, J. Tumlin, R. Van Vollenhoven, J. Varga, A. Vijayan, M. Vilardell-Tarres, D. Wallace, C. Weaver, M. Zummer

Research output: Contribution to journalArticle

Abstract

Objective. To examine the relationship between changes in anti-double-stranded DNA (anti-dsDNA) antibody levels and the risk of renal flare in patients with systemic lupus erythematosus (SLE), using data from 2 randomized, controlled trials. Methods. Analyses were based on 487 patients with SLE and a history of lupus nephritis who had an anti-dsDNA antibody titer ≥15 IU/ml at baseline, as measured by Farr assay. Results are presented for the combined population of patients, the placebo arms, and the drug treatment arms in which a dsDNA-based bioconjugate (abetimus sodium; LJP 394) was used. Results. Changes in anti-dsDNA antibody levels were inversely correlated with changes in the C3 level (P < 0.0001 in both trials). Cox proportional hazards regression models showed that changes in anti-dsDNA antibody levels correlated with the risk of renal flare. The models predicted that a point estimate of a 50% reduction in anti-dsDNA antibody levels is associated with a 52% reduction (95% confidence interval [95% CI] 26-68%, nominal P = 0.0007) and a 53% reduction (95% CI 33-69%, nominal P < 0.0001) in the risk of renal flare in the 2 trials, respectively. In the 2 trials, the incidence of renal flare was lower in patients with sustained reductions in anti-dsDNA antibodies (3.0% and 4.1%, respectively) than in patients with stable or increasing antibody levels (21.3% and 20.3%, respectively). Conclusion. Changes in anti-dsDNA antibody levels were directly correlated with the risk of renal flare and inversely correlated with changes in the C3 level. Reducing anti-dsDNA antibody levels may represent a therapeutic objective in SLE patients with lupus nephritis, because it is associated with a reduced risk of renal flare.

Original languageEnglish (US)
Pages (from-to)1129-1137
Number of pages9
JournalArthritis and rheumatism
Volume52
Issue number4
DOIs
StatePublished - Apr 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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    Linnik, M. D., Hu, J. Z., Heilbrunn, K. R., Strand, V., Hurley, F. L., Joh, T., Alarcón-Segovia, D., Appel, G., Aranow, C., Ballou, S., Becker, M. A., Becker, N., Belmont, M. H., Bohan, A., Boling, E. P., Bombardieri, S., Brelsford, W. G., Buyon, J. P., Cardiel, M. H., ... Zummer, M. (2005). Relationship between anti-double-stranded DNA antibodies and exacerbation of renal disease in patients with systemic lupus erythematosus. Arthritis and rheumatism, 52(4), 1129-1137. https://doi.org/10.1002/art.20980