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Antithyroperoxidase Antibody-Dependent Cytotoxicity in Autoimmune Thyroid Disease

Centre National de la Recherche Scientifique (S.A.R., B.N., F.C., S.P.-R.), Unit Mixté de Recherche 5232, Faculté de Pharmacie, 34093 Montpellier, France; and Institut National de la Santé et de la Recherche Médicale U860 (B.R.), Centre Régional de Lutte Contre le Cancer, Val d’Aurelle, Paul Lamarque, 34298 Montpellier, France

Address all correspondence and requests for reprints to: Dr. Sylvie Peraldi-Roux, Centre National de la Recherche Scientifique, Unit Mixté de Recherche 5232, Faculté de Pharmacie, 15 Avenue Charles Flahaut, 34093 Montpellier Cedex 5, France. E-mail: sylvie.roux{at}univ-montp1.fr.

Context: Thyroid antibody-dependent cytotoxicity has been reported in autoimmune thyroid disease (AITD). Indeed, the role of thyroperoxidase (TPO) autoantibodies (aAbs) in complement-mediated damage by binding to TPO expressed on the surface of human thyroid cells was demonstrated, whereas their activity in antibody-dependent cell cytotoxicity (ADCC) is not well established.

Objective: The aim of this study was to define the partners involved in antibody and complement-dependent cytotoxicity (CDC) in AITD and characterize which effector cells are involved in cytotoxicity mediated by anti-TPO aAbs using a chromium release assay.

Results: The relative capability of anti-TPO aAbs to mediate ADCC using human thyroid cells in culture varies from 11 to 74.5%, depending on the effectors cells used. The human monocyte cell line HL60 gives a better lysis than the THP-1 cell line as effector cells. It seems obvious that the mechanism of ADCC is mediated quite exclusively by FcRI. Indeed, the two effector cell lines differ by the level of the FcRI expression (91.83% for HL-60 cells and 22.55%t for the THP-1). In addition to ADCC, the anti-TPO aAbs mediate the destruction of thyrocytes by CDC (56%).

Conclusions: These results demonstrate that anti-TPO aAbs can damage cultured thyroid cells by ADCC and CDC mechanisms. The monocytes, via their FcRI, are important effector cells in ADCC mediated by anti-TPO aAbs and may contribute with T cells to the destruction of thyroid gland in AITD.