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Proteinase-3 Antineutrophil Cytoplasm Antibody Positivity in Patients Without Primary Systemic Vasculitis

McAdoo, Stephen Paul MBBS*; Hall, Angela MSc; Levy, Jeremy PhD*; Salama, Alan D. PhD; Pusey, Charles D. DSc*

JCR: Journal of Clinical Rheumatology: October 2012 - Volume 18 - Issue 7 - p 336–340
doi: 10.1097/RHU.0b013e31826d2005
Original Articles

Objectives Antineutrophil cytoplasm antibodies (ANCAs) are useful diagnostic markers in vasculitis. Historical data have suggested the combination of cytoplasmic (C-ANCA) staining with antibodies specific for proteinase 3 (PR3-ANCA) is 99% to 100% specific for granulomatosis with polyangiitis. We aimed to establish the frequency and associations of PR3-ANCA in patients without primary systemic vasculitis using current methods in our laboratory.

Methods This was a retrospective review of all patients identified as C-and PR3-ANCA positive as determined by indirect immunofluorescence and Luminex testing, respectively, in our laboratory over a 6-month period.

Results One hundred ninety-four patients were positive for both C- and PR3-ANCA. One hundred seventy-five patients had primary ANCA-associated vasculitis (AAV). Nineteen patients (9.7%) were C- and PR3-ANCA positive but without AAV. Clinical associations included infections, other autoimmune disorders, and malignancy. PR3-ANCA titer ranged from 31 to 278 U/mL (reference range, 0–25 U/mL). Three patients became PR3-ANCA negative after treatment of associated conditions. One patient went on to develop AAV 6 months after the study period.

Conclusions We detected a higher than expected frequency (9.7%) of “incidental” C- and PR3-ANCA. Several factors may be contributing, including the occurrence of ANCAs in other inflammatory states, the increased use of ANCA testing in unselected populations with low clinical suspicion of AAV, recent changes to detection methods for ANCA, and the probability that circulating ANCAs predate onset of clinical disease. Our data underscore the need to secure tissue diagnosis in AAV and to exclude other underlying conditions such as infection. In addition, patients with unexplained ANCAs should be followed up because they are at risk of developing disease over time.

From the *Imperial College Kidney and Transplant Institute; †Department of Clinical Immunology, Chelsea and Westminster Hospital; and ‡Centre for Nephrology, University College London, London, UK.

A.D.S. and C.D.P. contributed equally to this work.

Elements of this work were presented as oral communications at both the American Society of Nephrology Renal Week Conference 2010 and the 15th International ANCA and Vasculitis Workshop 2011. It has not been published in whole or part elsewhere.

Support was received from the NIHR Imperial College Biomedical Research Centre. Dr McAdoo is in receipt of a Medical Research Council Clinical Research Training Fellowship.

The authors declare no conflict of interest.

Correspondence: Stephen Paul McAdoo, MBBS, Imperial College Kidney and Transplant Institute, 9th Floor Commonwealth Bldg, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN. E-mail:

© 2012 Lippincott Williams & Wilkins, Inc.