Antithyroperoxidase Antibody-Dependent Cytotoxicity in Autoimmune Thyroid Disease

Rebuffat, Sandra A.; Nguyen, Brigitte; Robert, Bruno; Castex, Françoise; Péraldi-Roux, Sylvie

doi:10.1210/jc.2007-2042

Cited by 64 publications

(60 citation statements)

References 25 publications

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“…We previously showed that TPO aAbs are, through both ADCC and CDC, able to damage human thyroid cells on binding to TPO expressed on the cell surface (Rebuffat et al, 2008). In this study, we hypothesised that human recombinant anti-TPO aAbs could be used to destroy thyroid tumour cells and thus to develop a complementary therapeutic approach in thyroid cancers.…”

Section: Discussionmentioning

confidence: 95%

“…The expression of CD14, CD16 (FcgRIII), CD32 (FcgRII), CD64 (FcgRI) on the surface of the different effector cells (HL-60 and PBMC) was investigated using fluorescein-conjugated anti-human CD Ab (Miltenyi Biotech, Bergisch Gladbach, Germany and Pharmingen, Becton Dickinson, Franklin Lakes, NJ, USA) and analysed by flow cytometry analysis as previously described (Rebuffat et al, 2008). Monocytes and lymphocytes present in PBMC were identified by size/structure analysis.…”

Section: Cellsmentioning

confidence: 99%

“…Antibody-dependent cell-mediated cytotoxicity assays were carried out using the standard 51 Cr release assay (Rebuffat et al, 2008). Target cells (NPA cell line) were removed from culture flasks using HEPES -EDTA buffer, rinsed and aliquots (B10 6 cells) incubated (371C, 60 min, 5% CO 2 ) in culture medium 100 mCi 51 Cr.…”

Section: In Vitro Antibody-dependent Cell-mediated Cytotoxicity Assaymentioning

confidence: 99%

“…FcgRI (CD64) (the high-affinity IgG receptor), FcgRIIa (CD32) and FcgRIII (CD16) (the low-affinity IgG receptor) are activating receptors present on a wide range of myeloid cells (monocytes, macrophages, dendritic cells, neutrophils and natural killer (NK) cells). As we previously showed (Rebuffat et al, 2008) that monocytes are potential effector cells in AITD, the monocyte cell line HL-60 and PBMC were chosen as effector cells for cytotoxic assays. We characterised these cells regarding monocytes surface markers such as CD14 and FcgR expression.…”

Section: Thyroid Cancer and Effector Cell Lines Characterisationmentioning

confidence: 99%

“…Hashimoto's thyroiditis is characterised by glandular hypofunction, destruction of thyroid cells and production of an immunoglobulin G (IgG) response directed against TPO. Anti-TPO aAbs are invaluable markers of thyroid autoimmune response and have been shown to exert both in vitro and in vivo cytotoxic functions such as C3 complement activation (Wadeleux et al, 1989;Chiovato et al, 1993;Parkes et al, 1994) and antibody-dependent cell-mediated cytotoxicity (ADCC) (Bogner et al, 1989;Rodien et al, 1996;Guo et al, 1997;Metcalfe et al, 1997;Rebuffat et al, 2008). These effects probably participate in the maintenance and amplification of thyroid cell destruction in Hashimoto's disease.…”

mentioning

confidence: 99%

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Human recombinant anti-thyroperoxidase autoantibodies: in vitro cytotoxic activity on papillary thyroid cancer expressing TPO

Rebuffat¹,

Morin²,

Nguyen³

et al. 2010

Br J Cancer

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BACKGROUND: Thyroid cancers are difficult to treat due to their limited responsiveness to chemo-and radiotherapy. There is thus a great interest in and a need for alternative therapeutic approaches. RESULTS: We studied the cytotoxic activity of anti-thyroperoxidase autoantibodies (anti-TPO aAbs, expressed in baculovirus/insect cell (B4) and CHO cells (B4 0 ) or purified from patients' sera) against a papillary thyroid cancer (NPA) cell line. Anti-TPO aAbs from patients' sera led to a partial destruction of NPA cell line by complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) and exhibited an anti-proliferative activity. Comparison of the cytotoxic activity of anti-TPO aAbs shows that B4 0 induced an anti-proliferative effect and a better ADCC than B4, but a lower one than anti-TPO aAbs from patients' sera. Antibody-dependent cell-mediated cytotoxicity was increased when human peripheral blood mononuclear cells were used as effector cells, suggesting that FcgRs, CD64, CD32 and CD16 are involved. Indeed, anti-TPO aAbs from patients' sera, but not B4 and B4 0 , exhibited CDC activity. CONCLUSIONS: These data indicate that anti-TPO aAbs display moderate ADCC and anti-proliferative activities on NPA cells; IgG glycosylation appears to be important for cytotoxic activity and ADCC efficiency depends on FcgR-bearing cells. Finally, recombinant human anti-TPO aAbs cannot yet be considered as an optimal tool for the development of a novel therapeutic approach for thyroid cancer.

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Section: Discussionmentioning

confidence: 95%

Section: Cellsmentioning

confidence: 99%

Section: In Vitro Antibody-dependent Cell-mediated Cytotoxicity Assaymentioning

confidence: 99%

Section: Thyroid Cancer and Effector Cell Lines Characterisationmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Human recombinant anti-thyroperoxidase autoantibodies: in vitro cytotoxic activity on papillary thyroid cancer expressing TPO

Rebuffat¹,

Morin²,

Nguyen³

et al. 2010

Br J Cancer

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COVID‐19‐induced autoimmune thyroiditis: Exploring molecular mechanisms

Mohammadi

Dua

Saghafi

et al. 2023

Journal of Medical Virology

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Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) damages multiple organs, including the thyroid, by direct invasion and cell entry via angiotensin‐converting enzyme 2 or indirectly by promoting excessive inflammation in the body. The immune system is a critical factor in antiviral immunity and disease progression. In the context of SARS‐CoV‐2 infection, the immune system may become overly activated, resulting in a shift from regulatory to effector responses, which may subsequently promote the development and progression of autoimmune diseases. The incidence of autoimmune thyroid diseases, such as subacute thyroiditis, Graves' disease, and Hashimoto's thyroiditis, increases in individuals with COVID‐19 infection. This phenomenon may be attributed to aberrant responses of T‐cell subtypes, the presence of autoantibodies, impaired regulatory cell function, and excessive production of inflammatory cytokines, namely interleukin (IL)‐6, IL‐1β, interferon‐γ, and tumor necrosis factor‐α. Therefore, insights into the immune responses involved in the development of autoimmune thyroid disease according to COVID‐19 can help identify potential therapeutic approaches and guide the development of effective interventions to alleviate patients' symptoms.

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Glycosylation in Autoimmune Diseases

Ząbczyńska

Link-Lenczowski

Pocheć

2021

Advances in Experimental Medicine and Biology

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Antithyroperoxidase Antibody-Dependent Cytotoxicity in Autoimmune Thyroid Disease

Abstract: 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.

Cited by 64 publications

References 25 publications

Human recombinant anti-thyroperoxidase autoantibodies: in vitro cytotoxic activity on papillary thyroid cancer expressing TPO

Human recombinant anti-thyroperoxidase autoantibodies: in vitro cytotoxic activity on papillary thyroid cancer expressing TPO

COVID‐19‐induced autoimmune thyroiditis: Exploring molecular mechanisms

Glycosylation in Autoimmune Diseases

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