Antineutrophil cytoplasmic antibodies reacting with human neutrophil elastase as a diagnostic marker for cocaine-induced midline destructive lesions but not autoimmune vasculitis
Article first published online: 9 SEP 2004
Copyright © 2004 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 50, Issue 9, pages 2954–2965, September 2004
How to Cite
Wiesner, O., Russell, K. A., Lee, A. S., Jenne, D. E., Trimarchi, M., Gregorini, G. and Specks, U. (2004), Antineutrophil cytoplasmic antibodies reacting with human neutrophil elastase as a diagnostic marker for cocaine-induced midline destructive lesions but not autoimmune vasculitis. Arthritis & Rheumatism, 50: 2954–2965. doi: 10.1002/art.20479
- Issue published online: 9 SEP 2004
- Article first published online: 9 SEP 2004
- Manuscript Accepted: 20 MAY 2004
- Manuscript Received: 10 OCT 2003
- Mayo Foundation
- Division of Pulmonology, Otto-von-Guericke University, Magdeburg, Germany
- NIH. Grant Numbers: HL-07897-03, R21-AI-47572, R01-AR-49806
- German Research Council. Grant Number: SFB571
- Robert N. Brewer Foundation
Human neutrophil elastase (HNE) and proteinase 3 (PR3) are structurally and functionally related. PR3 is the prominent target antigen for antineutrophil cytoplasmic antibodies (ANCAs) in Wegener's granulomatosis (WG). Reported frequencies of HNE ANCAs in WG and other autoimmune diseases range from 0% to 20%. We previously detected HNE ANCAs in patients with cocaine-induced midline destructive lesions (CIMDL). We tested the hypothesis that discrepancies in the reported frequencies of HNE ANCAs in patients with vasculitis may be related to differences in detection methods, and that HNE ANCA may be a marker for CIMDL.
HNE ANCA reactivity in 25 patients with CIMDL was characterized and compared with that in a control cohort of 604 consecutive patients (64 with WG, 14 with microscopic polyangiitis [MPA], and 526 others) and 45 healthy volunteers. HNE ANCAs were measured by indirect immunofluorescence using a previously undescribed expression system for recombinant HNE and by direct and capture enzyme-linked immunosorbent assays using purified native HNE as target antigen.
Among patients with CIMDL, HNE ANCAs were detectable by 1 assay in 84%, by 2 assays in 68%, and by all 3 assays in 36%. Fifty-seven percent of HNE ANCA–positive CIMDL sera were also PR3 ANCA–positive by at least 1 assay. In contrast, only 8 (1.3%) of 604 control sera reacted with HNE in at least 1 assay, 3 (0.5%) reacted in 2 assays, and only 1 serum sample (0.16%) reacted in all 3 assays. Sera obtained from patients with WG or MPA were universally HNE ANCA–negative, as were sera obtained from healthy controls.
Optimal sensitivity for HNE ANCA requires multimodality testing. HNE ANCAs are frequent in CIMDL but not in other autoimmune diseases, including classic ANCA-associated vasculitis. HNE ANCAs may discriminate between CIMDL and WG, whereas a positive test result for PR3 ANCA may not.