Proteinase-3 antineutrophil cytoplasm antibody positivity in patients without primary systemic vasculitis

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.

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.

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.

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.