HDCN Abstract:  ASN Annual Meeting -- San Diego  

Owshalimpur D, Arbogast CB, Olson SW.

Chronological Serum Anti-Neutrophil Cytoplasmic Autoantibodies Prior to the Clinical Presentation of Wegener's Granulomatosis.

ASN Annual Meeting -- San Diego
J Am Soc Nephrol (Nov) 20:408A 2009

Background: The pathophysiology of Wegener's Granulomatosis (WG) has yet to be completely elucidated. Although in vitro, animal, and case report literature suggests a causal role for antinuclear cytoplasmic antibody (ANCA), clinical studies have confirmed only an association. Seronegative WG and a varied clinical spectrum of WG support a more complex disease mechanism.

Methods: We compared chronologic ANCA titers in 52 patients with known WG prior to disease presentation to those in 52 healthy age, sex, race, and age of serum sample matched controls using the Department of Defense Serum Repository (DoD SR). DoD SR comprises biannual serum samples dating back to 1990 from all active duty military personnel beginning on entrance to the military after a complete physical and laboratory evaluation.

Results: Forty-two percent of diseased subjects (DS) had a PR3 >6 U/mL prior to diagnosis vs 0% of healthy controls (HC) (p= 0.0001). There is a larger percent of DS than HC with an elevated PR3 >6 in the first quartile 1-239 days (64% vs. 0%; p=0.0001) and the second quartile 239-569 days prior to diagnosis (36.4% vs. 0%; p=0.0046). Fifty-four percent of DS had a PR3 >1 prior to diagnosis vs 2% in HC (p <0.0001). The sensitivity and specificity of an index serum sample PR3 >0 for future WG diagnosis were 71% and 54% respectively (PPV/NPV of 61%/65%). The sensitivity and specificity of index serum sample PR3 >2 were 15% and 100% respectively (PPV/NPV of 15%/100%).

Conclusion: PR3 is significantly elevated up to 1.5 years prior to WG diagnosis. A stable detectable PR3 level of >1 is associated with a significant increased future incidence of WG. Data suggests a 'two hit' theory with a baseline antibody production capability exacerbated by a secondary stimulus triggering pathologic antibody levels and clinical disease.

© Copyright 2009-2010 American Society of Nephrology.Reproduced with permission.
Until September of 2010 all ASN abstracts from the 2009 Annual Meeting are available at this link.

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