The Prevalence and Target Antigens of Antithyroid Drugs Induced Antineutrophil Cytoplasmic Antibodies (ANCA) in Chinese Patients with Hyperthyroidism

Abstract

Objective: Antithyroid drugs such as propylthiouracil (PTU) and methimazole (MMI) are common medications in Chinese patients with hyperthyroidism and PTU‐induced antineutrophil cytoplasmic antibody (ANCA) positive vasculitis has been reported. The current cross‐sectional study aimed to investigate the prevalence and the target antigens of ANCA in Chinese patients with hyperthyroidism pre‐ and post‐antithyroid medication therapy. Methods: Sera from 216 patients with hyperthyroidism in our hospital were collected from January to July in 2002. Patients were divided into four groups: untreated (n = 34); treated with PTU (n = 62); treated with MMI (n = 77); and treated with both PTU and MMI (n = 43). Indirect immunofluorescence (IIF) assay was used to detect ANCA and ANA. Antigen‐specific ELISAs were used to detect antigen specificities. The known antigens included myeloperoxidase (MPO), proteinase 3 (PR3), human leukocyte elastase (HLE), lactoferrin, bactericidal/permeability‐increasing protein (BPI), cathepsin G and azurocidin. Results: 33/216 sera were IIF positive, 20 of the 33 samples were ANCA positive, 11 samples were ANA positive, and two samples were both P‐ANCA and ANA positive. The prevalence of positive ANCA in patients receiving PTU (14/62, 22.6%) was significantly higher than that of untreated patients (1/34, 2.9%) and patients treated with MMI (0/77, 0), P < 0.017. Of the 22 IIF‐ANCA positive samples, 12 (54.5%) sera recognized lactoferrin, seven (31.8%) sera recognized HLE, four sera recognized MPO and azurocidin respectively, three sera recognized PR3 and cathepsin G respectively, and one serum recognized BPI. Six of the 22 (27.3%) patients with ANCA positive had clinical evidence of vasculitis. All patients with MPO‐ANCA and two of the three patients with PR3‐ANCA had clinical vasculitis. Conclusion: PTU is associated with the production of ANCA in patients with hyperthyroidism. PTU‐induced ANCA are due to polyclonal activation of B cells. Anti‐MPO and anti‐PR3 antibodies may associate the occurrence of clinical vasculitis.