title: Elevated subclinical double-stranded DNA antibodies and future proliferative lupus nephritis.
abstract: OBJECTIVE
  Elevated anti-double-stranded DNA (dsDNA) antibody and C-reactive protein are associated with proliferative lupus nephritis (PLN). Progression of quantitative anti-dsDNA antibody in patients with PLN has not been compared with that in patients with systemic lupus erythematosus (SLE) without LN before diagnosis. The temporal relationship between anti-dsDNA antibody and C-reactive protein elevation has also not been evaluated.
  
  
  METHODS
  This case-control Department of Defense Serum Repository (established in 1985) study compared longitudinal prediagnostic quantitative anti-dsDNA antibody and C-reactive protein levels in 23 patients with biopsy-proven PLN (Walter Reed Army Medical Center, 1993-2009) with levels in 21 controls with SLE but without LN matched for patient age, sex, race, and age of serum sample. The oldest (median, 2601 days; 25%, 1245 days, 75%, 3075 days), the second to last (368; 212, 635 days), and the last (180; 135, 477 days) serum sample before diagnosis were analyzed.
  
  
  RESULTS
  More patients with PLN had an elevated anti-dsDNA antibody level than did the matched controls at any point (78% versus 5%; P<0.001), <1 year (82% versus 8%; P<0.001), 1-4 years (53% versus 0%; P<0.001), and >4 years (33% versus 0%; P=0.04) before diagnosis. A rate of increase >1 IU/ml per year (70% versus 0%; P<0.001) was most specific for PLN. The anti-dsDNA antibody levels increased before C-reactive protein did in most patients with an antecedent elevation (92% versus 8%; P<0.001).
  
  
  CONCLUSIONS
  Elevated anti-dsDNA antibody usually precedes both clinical and subclinical evidence of proliferative LN, which suggests direct pathogenicity. Absolute anti-dsDNA antibody level and rate of increase could better establish risk of future PLN in patients with SLE.
authors.affiliation: Walter Reed National Military Medical Center, and, †Uniformed Service University of the Health Sciences, Bethesda, Maryland, ‡Madigan Army Medical Center, Tacoma, Washington.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Olson
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Lee
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Prince
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Baker
authors.forename: Patricia
authors.initials: P
authors.lastname: Papadopoulos
authors.forename: Jess
authors.initials: J
authors.lastname: Edison
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Abbott
mesh_terms: D000328:Adult; D000974:Antibodies, Antinuclear / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D004247:DNA / Q000276:immunology*; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008181:Lupus Nephritis / Q000209:etiology / Q000276:immunology*; D008297:Male; D012189:Retrospective Studies
chemical_list: D000974:Antibodies, Antinuclear; D002097:C-Reactive Protein; D004247:DNA