Exploratory Study of Clinical Factors Associated with MPO-ANCA Positivity in Nontuberculous Mycobacterial Pulmonary Disease

Background/Objectives: Nontuberculous mycobacterial pulmonary disease (NTM-PD) has been associated with myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)-positive ANCA-associated vasculitis (AAV). However, clinical factors associated with MPO-ANCA positivity in patients with NTM-PD remain unclear. This study determined the frequency of MPO-ANCA positivity among tested patients with NTM-PD and explored the clinical factors associated with MPO-ANCA positivity. Methods: This study retrospectively analyzed patients aged ≥15 years old with NTM-PD who were treated at Tokyo Shinagawa Hospital and underwent MPO-ANCA testing between April 2020 and March 2024. Clinical data, including nontuberculous mycobacterial species, serum Mycobacterium avium complex (MAC) antibody titers, radiographic findings, and nodule, infiltration/consolidation, cavity, and ectasis scores, were collected from their electronic medical records. Patients were classified into MPO-ANCA-positive and negative groups, and clinical factors were compared. Results: Among 109 patients with NTM-PD, 49 underwent testing for MPO-ANCA and proteinase 3 (PR3)-ANCA. MPO-ANCA was positive in five patients (10.2%), whereas PR3-ANCA was positive in one (2.0%). Among the five MPO-ANCA-positive patients, three had MAC antibody titers above the upper limit of measurement (>10 U/mL), and one developed AAV with biopsy-proven pauci-immune crescentic glomerulonephritis and mononeuritis multiplex. The MAC antibody titer was significantly higher in the MPO-ANCA-positive group than in the MPO-ANCA-negative group [10.0 (3.89–10.0) vs. 1.92 (0.19–6.19) U/mL, p = 0.038]. Conclusions: MPO-ANCA positivity was observed in a subset of tested patients with NTM-PD and was associated with higher MAC antibody titers. These findings suggest that chronic MAC-related antigen exposure or local pulmonary disease activity in NTM-PD may be associated with MPO-ANCA positivity.