Xavier Bossuyt1,2, Niels Rasmussen3, Pieter van Paassen4, Bernard Hellmich5,6, Bo Baslund7, Pieter Vermeersch2,8, Daniel Blockmans1,9, Jan-Willem Cohen Tervaert10, Elena Csernok5,6, Jan Damoiseaux11. 1. Department of Microbiology and Immunology, KU Leuven. 2. Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium. 3. Department of Autoimmunology and Biomarkers, Statens Seruminstitute, Copenhagen, Denmark. 4. Department of Internal Medicine, Section Nephrology and Immunology, Maastricht University Medical Center, Maastricht, The Netherlands. 5. Department of Internal Medicine, Rheumatology and Immunology, University Teaching Hospital Kirchheim. 6. Vasculitis-Center Tübingen-Kirchheim, Kirchheim, Germany. 7. Department of Rheumatology, Rigshospitalet, Copenhagen, Denmark. 8. Department of Cardiovascular Sciences, KU Leuven. 9. General Internal Medicine, University Hospitals Leuven, Leuven, Belgium. 10. Faculty of Health, Medicine and Life Sciences, Maastricht University. 11. Central Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, The Netherlands.
Abstract
Objective: The objective of this multicentre study was to improve the clinical interpretation of PR3- and MPO-ANCAs as an adjunct for the diagnosis of ANCA-associated vasculitis (AAV) by defining thresholds and test result intervals based on predefined specificities and by calculating test result interval-specific likelihood ratios (LRs). Methods: Eight different PR3- and MPO-ANCA immunoassays from seven companies were evaluated using 251 diagnostic samples from AAV patients and 924 diseased controls. Results: Thresholds for antibody levels were determined based on predefined specificities (95, 97.5, 99 and 100%) and used to delimit test result intervals. Test result interval-specific LRs were determined. For all assays, the LR for AAV increased with increasing antibody level. For all but one immunoassay, high antibodies levels (associated with LR >55) were found in a substantial fraction (>65%) of patients. The area under the curve (AUC) of receiver operating characteristics analysis of a diagnostic approach in which positive results were confirmed by IIF or another immunoassay was not substantially higher than the AUC of performing immunoassay only. The highest AUC was found when immunoassay was combined with another immunoassay or with IIF. Conclusion: To diagnose AAV based on PR3- and MPO-ANCA, it is useful to define thresholds for antibody levels and to assign test result interval-specific LRs. Higher antibody levels are associated with a higher likelihood for disease. Such information improves clinical interpretation.
Objective: The objective of this multicentre study was to improve the clinical interpretation of PR3- and MPO-ANCAs as an adjunct for the diagnosis of ANCA-associated vasculitis (AAV) by defining thresholds and test result intervals based on predefined specificities and by calculating test result interval-specific likelihood ratios (LRs). Methods: Eight different PR3- and MPO-ANCA immunoassays from seven companies were evaluated using 251 diagnostic samples from AAV patients and 924 diseased controls. Results: Thresholds for antibody levels were determined based on predefined specificities (95, 97.5, 99 and 100%) and used to delimit test result intervals. Test result interval-specific LRs were determined. For all assays, the LR for AAV increased with increasing antibody level. For all but one immunoassay, high antibodies levels (associated with LR >55) were found in a substantial fraction (>65%) of patients. The area under the curve (AUC) of receiver operating characteristics analysis of a diagnostic approach in which positive results were confirmed by IIF or another immunoassay was not substantially higher than the AUC of performing immunoassay only. The highest AUC was found when immunoassay was combined with another immunoassay or with IIF. Conclusion: To diagnose AAV based on PR3- and MPO-ANCA, it is useful to define thresholds for antibody levels and to assign test result interval-specific LRs. Higher antibody levels are associated with a higher likelihood for disease. Such information improves clinical interpretation.
Authors: Justyna Fijolek; E Wiatr; V Petroniec; E Augustynowicz-Kopec; M Bednarek; D Gawryluk; K Roszkowski-Sliz Journal: Clin Rheumatol Date: 2019-07-23 Impact factor: 2.980