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 FcgammaRI. Indeed, the two effector cell lines differ by the level of the FcgammaRI 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 FcgammaRI, 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.
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 FcgammaRI. Indeed, the two effector cell lines differ by the level of the FcgammaRI 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 FcgammaRI, 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.
Authors: Tiphaine C Martin; Mirna Šimurina; Marta Ząbczyńska; Marina Martinic Kavur; Magdalena Rydlewska; Marija Pezer; Kamila Kozłowska; Andrea Burri; Marija Vilaj; Renata Turek-Jabrocka; Milena Krnjajić-Tadijanović; Małgorzata Trofimiuk-Müldner; Ivo Ugrina; Anna Lityńska; Alicja Hubalewska-Dydejczyk; Irena Trbojevic-Akmacic; Ee Mun Lim; John P Walsh; Ewa Pocheć; Tim D Spector; Scott G Wilson; Gordan Lauc Journal: Mol Cell Proteomics Date: 2020-02-05 Impact factor: 5.911
Authors: Aleksander Kuś; Konrad Szymański; Beata Jurecka-Lubieniecka; Edyta Pawlak-Adamska; Dorota Kula; Piotr Miśkiewicz; Marek Bolanowski; Rafał Płoski; Artur Bossowski; Jacek Daroszewski; Barbara Jarząb; Tomasz Bednarczuk Journal: J Hum Genet Date: 2016-11-10 Impact factor: 3.172
Authors: Nadia Sawicka-Gutaj; Ariadna Zybek-Kocik; Aleksandra Klimowicz; Michał Kloska; Dorota Mańkowska-Wierzbicka; Jerzy Sowiński; Marek Ruchała Journal: Int J Endocrinol Date: 2016-01-17 Impact factor: 3.257
Authors: Marlena Godlewska; Katarzyna D Arczewska; Magdalena Rudzińska; Anna Łyczkowska; Wanda Krasuska; Karolina Hanusek; Jean Ruf; Mirosław Kiedrowski; Barbara Czarnocka Journal: PLoS One Date: 2017-06-02 Impact factor: 3.240