Abstract Objectives Antineutrophil cytoplasmic antibodies (ANCA) are a key biomarker for ANCA-associated vasculitis (AAV), particularly microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Although indirect immunofluorescence (IIF) has traditionally been the reference technique, its diagnostic value in contemporary real-world practice remains uncertain. The aim of this study was to evaluate the diagnostic performance of IIF ANCA testing in routine clinical practice. Methods We conducted a retrospective study of all patients with an ANCA request at a tertiary hospital over a four-year period. All IIF-positive sera were subsequently tested for anti-PR3 and anti-MPO antibodies by chemiluminescent immunoassay (CLIA). Clinical data, test indication and final diagnoses were retrieved from electronic medical records. Results We included 5,157 patients and IIF was positive in 653 (12.7%): perinuclear ANCA (P-ANCA) in 17.9%, cytoplasmic ANCA (C-ANCA) in 13.3% and atypical ANCA (A-ANCA) in 68.8%. CLIA was negative in 97.3% of A-ANCA. AAV was diagnosed in 47 patients, and 42 (89.4%) had positive IIF. For GPA and MPA, IIF showed a sensitivity of 93% and specificity of 88%, with a very high negative predictive value (NPV) (99.9%) but low positive predictive value (PPV) (6.1%). Specificity improved to 96.8% when restricted to typical patterns (C-ANCA or P-ANCA) and to 99.6% when combined with positive CLIA results 20 IU/ml. Almost all AAV cases were diagnosed in patients with high pre-test probability (such as renal disease, lung infiltrates, or peripheral neuropathies) and interstitial lung disease was the most frequent non-AAV diagnosis in IIF-positive patients. Conclusions ANCA IIF retains good diagnostic efficiency and a very high NPV for GPA and MPA, but has low PPV, particularly when tested for nonspecific symptoms.
Loureiro-Amigo et al. (Tue,) studied this question.