title: Relation between asymptomatic proteinase 3 antibodies and future granulomatosis with polyangiitis.
abstract: OBJECTIVE
  The subclinical pathogenesis of granulomatosis with polyangiitis (GPA) has not been completely elucidated. Proteinase 3 (PR3) antibodies are strongly associated with GPA, but have not been evaluated before disease presentation.
  
  
  METHODS
  This was a retrospective case-control serum bank study in which PR3 antibodies and C-reactive protein (CRP) in up to three longitudinal serum samples for 27 GPA patients before diagnosis (1 day-19 years) were compared with 27 controls whose serum samples were matched for age, sex, and race. This study analyzed all patients with American College of Rheumatology criteria-confirmed disease identified in the Department of Defense electronic medical records between 1990 and 2008.
  
  
  RESULTS
  A greater percentage of GPA patients had at least one elevated PR3 antibody level (≥6 U/ml) as well as at least one detectable PR3 antibody level (>1 U/ml) before diagnosis compared with matching controls (63% [17 of 27] versus 0% [0 of 27], P<0.001; and 85% [23 of 27] versus 4% [1 of 27], P<0.001, respectively). A greater percentage of GPA patients had a >1 U/ml per year rate of increase in PR3 antibody level compared with matching controls (62% [21 of 26] versus 0% [0 of 26], P<0.001). PR3 antibody more frequently became elevated before CRP (67% [12 of 18] versus 33% [6 of 18], P=0.04).
  
  
  CONCLUSIONS
  Subclinical PR3 antibody presence, trajectory, and temporal relationship to CRP associates with the future diagnosis of GPA. This data set further elucidates the pathogenesis of GPA.
authors: Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA. stephen.w.olson@health.mil
authors: Stephen W
authors: SW
authors: Olson
authors: David
authors: D
authors: Owshalimpur
authors: Christina M
authors: CM
authors: Yuan
authors: Charles
authors: C
authors: Arbogast
authors: Thomas P
authors: TP
authors: Baker
authors: David
authors: D
authors: Oliver
authors: Kevin C
authors: KC
authors: Abbott
mesh_terms: D000293:Adolescent; D000328:Adult; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D053146:Myeloblastin / Q000276:immunology*; D012189:Retrospective Studies
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D002097:C-Reactive Protein; D053146:Myeloblastin
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