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Frequency of Antineutrophil Cytoplasmic Antibody in Graves’ Disease Patients Treated with Methimazole

Rheumatology Section (M.G., M.V.-R., A.O.), Endocrinology Service (I.S., J.L.R.), Epidemiology Unit (J.R.), and Immunology Unit, Laboratori d’Immunobiologia per a la Recerca i Aplicacions Diagnòstiques (M.J.), Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Spain

Address all correspondence and requests for reprints to: Mònica Gumà, Immunology, Universitat Pompeu Fabra, C/Dr Aiguader 80, 08003 Barcelona, Spain. E-mail: monica.guma{at}cexs.upf.es.

Retrospective studies have shown antineutrophil cytoplasmic antibody (ANCA) positivity in patients treated for Graves’ hyperthyroidism; ANCA has been attributed to either antithyroid drugs or to the disease itself.

The aim of this study was to determine ANCA in Graves’ disease patients at diagnosis and after treatment with methimazole and to evaluate the relationship between ANCA and hyperthyroidism evolution.

Thirty patients recently diagnosed with Graves’ hyperthyroidism were prospectively studied. ANCA were determined by indirect immunofluorescence. ANCA autoantibodies against specific antigens (proteinase 3, myeloperoxidase, bactericidal/permeability-increasing protein (BPI), cathepsin, lysozyme, elastase, and lactoferrin) were detected by ELISA. The median observation period was 22 months. Kaplan-Meier analysis was performed to identify ANCA as an outcome variable.

Twenty patients (67%) were ANCA positive before the onset of treatment, and four (19%) remained positive after 1 yr of antithyroid drug treatment. No differences were observed in any clinical or analytical features between patients with or without positive ANCA. Before treatment, BPI-positive patients required radioiodine treatment or presented relapse more rapidly than BPI-negative patients (log-rank test P < 0.0002).

Patients with Graves’ hyperthyroidism show positive ANCA before medical treatment, which points to a relationship with the autoimmune disease itself. Our results suggest that BPI-positive patients tend to relapse with antithyroid medication.

This work was supported by a grant from the Catalan Society for Rheumatology.

Abbreviations: ANA, Antinuclear antibodies; ANCA, antineutrophil cytoplasmic antibody or antibodies; BPI, bactericidal/permeability-increasing protein; c-ANCA, cytoplasmic fluorescence staining pattern ANCA; dsDNA, double-stranded DNA; FT₄, free T₄; GB, Graves-Basedow; IIF, indirect immunofluorescence; MMI, methimazole; MPO, myeloperoxidase; p-ANCA, perinuclear staining pattern ANCA; PR3, proteinase 3; TG, thyroglobulin; TPO, thyroid peroxidase; TRAb, TSH receptor antibody; TSH-R, TSH receptor; x-ANCA, atypical ANCA.

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