The prevalence and target antigens of antithyroid drugs induced antineutrophil cytoplasmic antibodies (ANCA) in Chinese patients with hyperthyroidism

Endocr Res. 2004 May;30(2):205-13. doi: 10.1081/erc-120037729.

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.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Antineutrophil Cytoplasmic / blood*
  • Antibodies, Antineutrophil Cytoplasmic / immunology*
  • Antithyroid Agents / therapeutic use*
  • Asian Continental Ancestry Group*
  • Cross-Sectional Studies
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes / immunology*
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Hyperthyroidism / drug therapy*
  • Hyperthyroidism / immunology*
  • Methimazole / therapeutic use
  • Middle Aged
  • Propylthiouracil / therapeutic use

Substances

  • Antibodies, Antineutrophil Cytoplasmic
  • Antithyroid Agents
  • Epitopes
  • Methimazole
  • Propylthiouracil