Jan Damoiseaux1, Elena Csernok2, Niels Rasmussen3, Frank Moosig4, Pieter van Paassen5, Bo Baslund6, Pieter Vermeersch7,8, Daniel Blockmans9, Jan-Willem Cohen Tervaert10, Xavier Bossuyt11,12. 1. Central Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, The Netherlands. 2. Department of Rheumatology and Immunology, Klinikum Bad Bramstedt, Bad Bramstedt, Germany. 3. Department of Autoimmune Serology, Statens Seruminstitute, Copenhagen, Denmark. 4. Rheumazentrum Schleswig-Holstein Mitte, Neumünster, Germany. 5. Department of Internal Medicine, Section Nephrology and Immunology, Maastricht University Medical Center, Maastricht, The Netherlands. 6. Department of Rheumatology, Rigshospitalet, Copenhagen, Denmark. 7. Clinical Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium. 8. Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium. 9. Clinical Department of General Internal Medicine, Research Department of Microbiology and Immunology, Laboratory of Clinical Infectious and Inflammatory Disorders, University Hospitals Leuven, Leuven, Belgium. 10. Maastricht University, Maastricht, The Netherlands. 11. Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium. 12. Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium.
Abstract
OBJECTIVE: This multicentre study was performed to evaluate the diagnostic accuracy of a wide spectrum of novel technologies nowadays available for detection of myeloperoxidase (MPO) and proteinase 3 (PR3)-antineutrophil cytoplasmic antibodies (ANCAs). METHODS: Sera (obtained at the time of diagnosis) from 251 patients with ANCA-associated vasculitis (AAV), including granulomatosis with polyangiitis and microscopic polyangiitis, and from 924 disease controls were tested for the presence of cytoplasmic pattern/perinuclear pattern and atypical ANCA (A-ANCA) by indirect immunofluorescence (IIF) (at two sites) and for the presence of PR3-ANCA and MPO-ANCA by eight different immunoassays. RESULTS: The area under the curve (AUC) of the receiver operating characteristic curve to discriminate AAV from controls was 0.923 (95% CI 0.902 to 0.944) and 0.843 (95% CI 0.814 to 0.871) for the two IIF methods. For the antigen-specific immunoassays, the AUC varied between 0.936 (95% CI 0.912 to 0.960) and 0.959 (95% CI 0.941 to 0.976), except for one immunoassay for which the AUC was 0.919 (95% CI 0.892 to 0.945). CONCLUSIONS: Our comparison of various ANCA detection methods showed (i) large variability between the two IIF methods tested and (ii) a high diagnostic performance of PR3-ANCA and MPO-ANCA by immunoassay to discriminate AAV from disease controls. Consequently, dual IIF/antigen-specific immunoassay testing of each sample is not necessary for maximal diagnostic accuracy. These results indicate that the current international consensus on ANCA testing for AAV needs revision. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
OBJECTIVE: This multicentre study was performed to evaluate the diagnostic accuracy of a wide spectrum of novel technologies nowadays available for detection of myeloperoxidase (MPO) and proteinase 3 (PR3)-antineutrophil cytoplasmic antibodies (ANCAs). METHODS: Sera (obtained at the time of diagnosis) from 251 patients with ANCA-associated vasculitis (AAV), including granulomatosis with polyangiitis and microscopic polyangiitis, and from 924 disease controls were tested for the presence of cytoplasmic pattern/perinuclear pattern and atypical ANCA (A-ANCA) by indirect immunofluorescence (IIF) (at two sites) and for the presence of PR3-ANCA and MPO-ANCA by eight different immunoassays. RESULTS: The area under the curve (AUC) of the receiver operating characteristic curve to discriminate AAV from controls was 0.923 (95% CI 0.902 to 0.944) and 0.843 (95% CI 0.814 to 0.871) for the two IIF methods. For the antigen-specific immunoassays, the AUC varied between 0.936 (95% CI 0.912 to 0.960) and 0.959 (95% CI 0.941 to 0.976), except for one immunoassay for which the AUC was 0.919 (95% CI 0.892 to 0.945). CONCLUSIONS: Our comparison of various ANCA detection methods showed (i) large variability between the two IIF methods tested and (ii) a high diagnostic performance of PR3-ANCA and MPO-ANCA by immunoassay to discriminate AAV from disease controls. Consequently, dual IIF/antigen-specific immunoassay testing of each sample is not necessary for maximal diagnostic accuracy. These results indicate that the current international consensus on ANCA testing for AAV needs revision. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Authors: Guillermo Carvajal Alegria; Pierre Gazeau; Sophie Hillion; Claire I Daïen; Divi Y K Cornec Journal: Clin Rev Allergy Immunol Date: 2017-10 Impact factor: 8.667