Yi Tong Vincent Aw¹, Jason Chun Lao^2,3, Richard Fulton², Jamma Li^1,3, Suran Fernando^1,2,3

¹Department of Clinical Immunology and Allergy, Royal North Shore Hospital, Sydney, Australia
²Immunology Laboratory, Royal North Shore Hospital/NSW Health Pathology, Sydney, Australia
³Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, Australia

Introduction: Many Australian laboratories perform Anti-neutrophil cytoplasmic Antibody (ANCA) testing following the 1999 international consensus statement¹ with indirect immunofluorescence, followed by anti-proteinase-3 (PR3) and anti-myeloperoxidase (MPO) immunoassay (non-gated strategy; NGS). The revised 2017 consensus statement recommends performing MPO/PR3 immunoassay after initial screening with a recommended gating strategy (RGS)², but the optimal gating strategy remains unclear. 

 

Method: Retrospective analysis was performed on consecutive ANCA tests done at Royal North Shore Hospital/NSW Health Pathology from 1^st January 2022 to 21^st March 2022. Performance characteristics for ANCA-associated vasculitis (AAV) diagnosis was determined for NGS, RGS and a novel classification criteria-based gating strategy (CCGS).

 

Results: 516 tests were included with 19 cases of active AAV. NGS approach had 57.7% positive predictive value (PPV), 99.2% negative predictive value (NPV), likelihood ratio (LR) + 35.7 and LR – 0.22. RGS approach had improved PPV (83.3%) and LR + (130.4), while maintaining high NPV (99.2%) and avoiding 79.8% of ANCA tests. CCGS performed the same as RGS approach but would have avoided 85.9% of ANCA tests. No cases of AAV were missed after 499 days median follow-up.

 

Conclusion: Application of the novel CCGS approach may potentially improve diagnostic performance and substantially reduce the number of ANCA tests performed.

References: 

1.     J. Savige, D. Gillis, E. Benson, D. Davies, V. Esnault, R.J. Falk, et al. International consensus statement on testing and reporting of antineutrophil cytoplasmic antibodies (ANCA). Am J Clin Pathol, 111 (4) (1999), pp. 507-513.

2.     X. Bossuyt, J.W. Cohen Tervaert, D. Blockmans, L.F. Flores-Suárez, L. Guillevin, et al. Revised 2017 international consensus on testing of ANCA in granulomatosis with polyangiitis and microscopic polyangiitis. Nat Rev Rheumatol, 13 (11) (2017), pp. 683-692.

 

Submitting author statement: The submitting author contributed to the study concept and design, data collection, analysis and writing. These elements were all original ideas of the submitting author. Generative AI was not used in the writing process.