title: Relationship between anti-double-stranded DNA antibodies and exacerbation of renal disease in patients with systemic lupus erythematosus.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: La Jolla Pharmaceutical Company, San Diego, California 92121, USA. linnik@ljpc.com
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Linnik
authors.forename: Jay Z
authors.initials: JZ
authors.lastname: Hu
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Heilbrunn
authors.forename: Vibeke
authors.initials: V
authors.lastname: Strand
authors.forename: Frank L
authors.initials: FL
authors.lastname: Hurley
authors.forename: Tenshang
authors.initials: T
authors.lastname: Joh
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000032:analysis*; D003404:Creatinine / Q000097:blood; D004247:DNA / Q000187:drug effects / Q000276:immunology*; D005260:Female; D006801:Humans; D008181:Lupus Nephritis / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009841:Oligonucleotides / Q000627:therapeutic use; D011507:Proteinuria; D012189:Retrospective Studies; D055502:Secondary Prevention; D013997:Time Factors
chemical_list: D000276:Adjuvants, Immunologic; D000974:Antibodies, Antinuclear; D009841:Oligonucleotides; D004247:DNA; D003404:Creatinine; C094104:abetimus