Simplifying ANCA-associated vasculitis classification with ANCA specificity: a retrospective analysis

Abstract

Objective: This study aimed to evaluate the utility of ANCA specificity as a primary criterion for classifying AAV subtypes to simplify the diagnostic process without compromising accuracy.

Methods: A retrospective cohort study was conducted involving 310 patients diagnosed with AAV between January 2015 and December 2023 across three tertiary care centers affiliated with Peking University. Patients were reclassified using three methods: the European Medicines Agency (EMA) algorithm, the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) criteria, and ANCA specificity-based classification. Concordance between classification systems was assessed using Cohen's kappa coefficients.

Results: ANCA specificity-based classification demonstrated substantial to almost perfect agreement with the 2022 ACR/EULAR criteria for MPA/MPO-AAV (kappa = 0.806) and GPA/PR3-AAV (kappa = 0.663). Many patients initially classified as GPA under the EMA algorithm were reclassified as MPA when using ANCA specificity. EGPA classification remained consistent across all methods (kappa = 0.725 between EMA and ACR/EULAR), suggesting that ANCA specificity is less critical for EGPA. The use of ANCA specificity simplified the classification process, aligning closely with the underlying pathophysiology of AAV subtypes.

Conclusion: ANCA specificity serves as a valuable adjunct in the classification of AAV, particularly for distinguishing between MPA and GPA. Utilizing ANCA serotypes can simplify the diagnostic process, potentially facilitating earlier diagnosis and targeted treatment. For EGPA, traditional classification criteria remain effective. Incorporating ANCA specificity into clinical practice may enhance diagnostic accuracy and improve patient outcomes in AAV management. Key Points • ANCA-based classification aligns strongly with the 2022 ACR/EULAR criteria for MPA and GPA, providing a simplified diagnostic approach. • Adopting this approach can streamline the classification process, reduce invasive procedures, and enable earlier diagnosis while maintaining high concordance with established systems.

Keywords: 2022 ACR/EULAR criteria; ANCA specificity; ANCA-associated vasculitis (AAV); Clinical utility; Diagnostic classification; EMA algorithm; Kappa statistics; MPO-ANCA; PR3-ANCA.

Fig. 1

Comparison of classification results between the EMA algorithm and the 2022 ACR/EULAR criteria. The flow diagram illustrates the reclassification of patients from the EMA algorithm to the 2022 ACR/EULAR criteria, highlighting the significant shift of patients from GPA to MPA classification. MPA, microscopic polyangiitis; GPA, granulomatosis with polyangiitis; EGPA, eosinophilic GPA

Fig. 2

Sankey diagram showing transitions between the EMA algorithm and 2022 ACR/EULAR criteria. The diagram visualizes the patient distribution changes when reclassified based on the 2022 ACR/EULAR criteria, demonstrating the discrepancies between traditional classifications. ANCA, antineutrophil cytoplasmic antibody; MPA, microscopic polyangiitis; GPA, granulomatosis with polyangiitis; EGPA, eosinophilic GPA

Fig. 3

Sankey diagram illustrating classification transitions among the EMA algorithm, 2022 ACR/EULAR criteria, and ANCA specificity. This comprehensive diagram shows the multi-dimensional classification transitions, emphasizing the alignment between ANCA specificity and the 2022 ACR/EULAR criteria. AAV, ANCA-associated vasculitis; ANCA, antineutrophil cytoplasmic antibody; MPA, microscopic polyangiitis; GPA, granulomatosis with polyangiitis; EGPA, eosinophilic GPA; MPO, myeloperoxidase; P, perinuclear; PR3, proteinase 3; C, cytoplasmic