Clinical research study
ANCA Are Detectable in Nearly All Patients with Active Severe Wegener’s Granulomatosis

https://doi.org/10.1016/j.amjmed.2006.08.016Get rights and content

Abstract

Background

The pathogenic significance of antineutrophilic cytoplasmic antibodies (ANCA) in Wegener’s granulomatosis is controversial. Their presence is influenced by the extent, severity, and activity of the disease at the time of sampling. The objective of this study was to determine the frequency of ANCA in patients with active Wegener’s granulomatosis and to assess the influence of disease severity on test results.

Methods

Baseline serum samples from the 180 participants in a multicentric prospective trial were tested for ANCA by indirect immunofluorescence, direct enzyme-linked immunosorbent assay (ELISA), and capture ELISA. Disease activity was measured using the Birmingham Vasculitis Activity Score for Wegener’s granulomatosis. All patients had active disease at enrollment. Patients were categorized as having severe (n = 128) or limited (n = 52) Wegener’s granulomatosis.

Results

When all ANCA detection methods were combined, 166 patients (92%) were ANCA positive, including 96% with severe disease and 83% with limited disease.

Conclusion

ANCA are detectable in nearly all patients with active severe Wegener’s granulomatosis, but approximately 1 of 5 patients with active limited disease are ANCA negative. Immunofluorescence and both direct and capture ELISAs are required for optimal detection, suggesting that ANCA are not recognized equally well by all testing methods.

Section snippets

Patients and Serum Samples

Samples used in this study were obtained from the Wegener’s Granulomatosis Etanercept Trial (WGET).13 The protocol for WGET was approved by the institutional review board at each participating center. Informed written consent was obtained from all participants. Full details of the study design have been published elsewhere.14 All patients met at least 2 of the 5 modified criteria of the American College of Rheumatology for the classification of Wegener’s granulomatosis14 and had active disease

Results

A description of baseline characteristics of the 180 patients constituting the WGET cohort has been published elsewhere.15 The mean (standard deviation) age was 47 (16) years, there were 108 (60%) men, and the majority (92%) were white. Eighty patients (44%) had newly diagnosed Wegener’s granulomatosis. The median (interquartile range) time since the onset of symptoms was 17 (5-50) months and since diagnosis was 5 (1-36) months. The median (interquartile range) BVAS/WG at entry was 6 (4-9).

At

Discussion

The results of this study indicate that when a multimodality ANCA testing approach is used, nearly all patients with active severe Wegener’s granulomatosis are ANCA positive. In those with active limited disease, ANCA was found in 83%. This study is unique in several respects. First, the WGET cohort is the largest cohort of patients with Wegener’s granulomatosis evaluated in a protocolized fashion. Second, disease activity was recorded with a standardized, validated instrument in all patients.13

Conclusion

Our study demonstrates that almost all patients with active severe Wegener’s granulomatosis have ANCA. A combination of immunofluorescence, direct ELISA, and capture ELISA seems to be required to ensure optimal detection of these antibodies, suggesting that ANCA are a heterogeneous group of antibodies that are not recognized equally well by all testing methods.

References (20)

There are more references available in the full text version of this article.

Cited by (232)

View all citing articles on Scopus

This study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health (NIH) R01-AR49806 (to U. S.), and funds from the Mayo Foundation. Dr Peikert was supported by NIH training grant T32-HL07897. The WGET trial was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH N01-AR92240 and the Office of Orphan Products, Food and Drug Administration (grant FD-R-001652), General Clinical Research Center Grants M01-RRO-00533 (Boston University), M01-RRO-0042 (The University of Michigan), MO1-RR-30 (Duke University), and M01-RRO-2719 (Johns Hopkins University School of Medicine), from the National Center for Research Resources/NIH. Drs Stone, Merkel, and St Clair were supported by National Institute of Arthritis and Musculoskeletal and Skin Diseases grants K24 AR049185-01, K24 AR2224-01A1, and K24 AR02126-04. Dr Stone is a Hugh and Renna Cosner Scholar in the Center for Innovative Medicine at the Johns Hopkins Bayview Medical Center.

These authors contributed equally and should be considered co-first authors.

View full text