Relation between asymptomatic proteinase 3 antibodies and future granulomatosis with polyangiitis

Background and objectives The subclinical pathogenesis of granulomatosiswith polyangiitis (GPA) has not been completely elucidated. Proteinase 3 (PR3) antibodies are strongly associated with GPA, but have not been evaluated before disease presentation. Design, setting, participants, & measurements This was a retrospective case-control serum bank study in which PR3 antibodies and C-reactive protein (CRP) in up to three longitudinal serumsamples for 27 GPApatients before diagnosis (1 day-19 years) were comparedwith 27 controlswhose serumsampleswerematched 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. ResultsAgreater percentage of GPApatients had at least one elevated PR3 antibody level (≥6 U/ml) as well as at least one detectable PR3 antibody level (>1U/ml) before diagnosis comparedwithmatching 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.