Antineutrophil cytoplasmic antibodies in patients with Graves’ disease: association of antimyeloperoxidase autoantibodies with propylthiouracil therapy

Abstract

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitic disorders have been reported in patients with Graves’ disease during propylthiouracil (PTU) therapy. To investigate whether ANCA are found in serum samples from patients with Graves’ disease, and whether PTU therapy is associated with ANCA positivity, levels of serum ANCA were examined in Graves’-disease patients receiving either PTU (n = 49) or 1-methyl-2-mercaptoimidazole (methimazole, MMI) (n = 50), and in untreated Graves’-disease patients (n = 32) by enzyme-linked immunosorbent assay (ELISA). Serum samples from patients with Hashimoto’s thyroiditis (n = 46) were also analyzed. Antimyeloperoxidase (MPO) autoantibodies (MPO-ANCA) were present in 10 (20.4%) of 49 Graves’-disease patients receiving PTU therapy, whereas MPO-ANCA were not detected in Graves’-disease patients receiving MMI, in untreated Graves’-disease patients, or in Hashimoto’s thyroiditis patients. The MPO-ANCA-positive sera showed a perinuclear staining pattern which was detected by indirect immunofluorescence microscopy using a human polymorphonuclear leukocyte–cytospin preparation. Furthermore, Western blot analysis revealed that MPO-ANCA in the Graves’-disease patients, as well as MPO-ANCA in patients with idiopathic pauci-immune necrotizing and crescentic glomerulonephritis, recognize the 105-kD protein of native MPO. These results indicate that MPO-ANCA in Graves’-disease patients are strongly associated with PTU therapy, and not simply related to the autoimmune thyroid disease. This study also suggests that the presence of MPO-ANCA alone may not be sufficient for the development of vasculitic disorders.