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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

164 Scopus citations

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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