Cytotoxic Assay of Circulating Thyroid Peroxidase Antibodies

Wadeleux, P.; Winand-Devigne, J.; Ruf, Jean; Carayon, Pierre; Winand, René

doi:10.3109/08916938909014701

Cited by 23 publications

(5 citation statements)

References 22 publications

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“…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.…”

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confidence: 99%

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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mentioning

confidence: 99%

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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“…TPO has been found to be implicated in thyroid cyloloxicity [9], but complement-dependent as well as antibody-dependent cell-mediated cytotoxieity has not yet been assigned to autoantibodies with clearly defined antigen specificity [23,24]. Seeking for such a pathophysiological role for TGPO auloantibodies, we measured TGPO autoantibodies in 50 human sera previously studied for their complement-dependent cytotoxicity on porcine thyroid cells.…”

Section: Discussionmentioning

confidence: 99%

“…and group 3 containing sera positive for TG and TPO autoantibodies. We used an additional series of 50 serum samples from patients with thyroid disorder, kindly provided by Dr R. Winand (Liege, Belgium) and tested for their complement-dependent eytotoxicity by 'H-ieucine incorporation in cultured porcine thyroid cells as previously described [9]. A control group was formed of six sera negative for TG and TPO autoantibodies provided by healthy women investigated for in vitro fertilization.…”

Section: Serum Samples From Patientsmentioning

confidence: 99%

“…In conirast, TG has been shown to induce experimental murine autoimmune thyroiditis depending on the choice of both mouse strain [6] and TG species [7]. TPO has only recently been identified as the thyroid microsomal antigen [8] and shown to be a putative target for complement-dependent cytotoxicity [9]. TPO from porcine thyroid was also found to induce experimental thyroiditis, but in mouse strains diflerent from those in which thyroiditis is induced by TG [10].…”

Section: Introductionmentioning

confidence: 99%

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Significance of thyroglobulin antibodies cross-reactive with thyroperoxidase (TGPO antibodies) in individual patients and immunized mice

Ruf

Ferrand

Durand‐Gorde

et al. 1993

Clinical and Experimental Immunology

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Thyroglobulin (TG) and thyroperoxidase (TPO), both involved in thyroid hormone synthesis, represent major autoantigens in thyroid autoimmune disease. Despite numerous studies, the emergence, pathophysiological significance and role of autoantibodies to TG and TPO remain elusive. The recent identification of a new category of thyroid-specific autoantibody interacting with both TG and TPO (TGPO autoantibodies) offers a new opportunity in the study of thyroid autoimmunity. To gain a better insight into the significance of these TGPO autoantibodies, measurement in individual samples appeared necessary. The unique property of TGPO autoantibodies, simultaneous binding to TG and TPO, was used to set up a sandwich method which combined coated TG and radio-iodinated TPO. This method was found to be strictly specific for TGPO autoantibodies and sensitive enough to assay TGPO autoantibodies in serum. In humans, TGPO autoantibodies were found in most of the sera with high TG and TPO autoantibody titres, but not in sera negative for TG autoantibodies, whatever the TPO autoantibody titre. Furthermore, high TGPO autoantibody titres were found in sera strongly cytotoxic for cultured porcine thyroid cells. However, significant correlation of TGPO autoantibody titre was observed neither with TG and TPO autoantibody titres (n = 48) nor with complement-dependent cytotoxicity (n = 50). TGPO antibody assay was also performed in individual plasma of CBA/J mice immunized with either human TG (n = 6) or human TPO (n = 6). Immunization with TG induced high levels of not only TG but also TGPO antibodies, which exhibited a strong reactivity for TPO and whose binding to TG and TPO was fully inhibited by TG. In contrast, immunization with TPO induced high levels of only specific TPO antibodies accompanied by low levels of specific TG antibodies. In this case TGPO antibodies were not detected. Of note, TG- and TPO-immunized mice mounted an immune response against their own TG, but did not exhibit histological signs of thyroiditis. Large panels of TG and TPO MoAbs were also investigated with this method: 18/25 TG MoAbs and only 1/13 TPO MoAbs were found cross-reactive. Taken together, these data provide evidence that TGPO antibodies are effectively present in individual patients and TG-immunized mice, are different from specific TG and TPO antibodies, and may derive from natural B cell repertoire by autoimmune processes involving TG and not TPO.

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“…It is believed that thyroid lesion is, in part, a consequence of complement fixation [2][3][4] and antibodydependent cell-mediated cytotoxicity (ADCC) [5][6][7][8] generated by TPOAb. Patients with HT have a great deal of clinical status; in general, it is an inconvertible process of evolving from euthyroidism to hypothyroidism.…”

Section: Introductionmentioning

confidence: 99%

Distribution of immunoglobulin G subclasses of anti-thyroid peroxidase antibody in sera from patients with Hashimoto's thyroiditis with different thyroid functional status

Xie

Gao

et al. 2008

Clinical and Experimental Immunology

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SummaryThe mechanism of disease progression in Hashimoto's thyroiditis (HT) is still unclear. Anti-thyroid peroxidase antibody (TPOAb), a diagnostic hallmark of HT, is principally of the immunoglobulin G (IgG) isotype, and it appears to be a response to thyroid injury. The aim of our study was to evaluate the distribution of IgG subclasses of TPOAb in sera from patients with HT with different thyroid functional status. Sera from 168 patients with newly diagnosed HT were collected and divided into three groups according to thyroid function: patients with hypothyroidism (n = 66), subclinical hypothyroidism (n = 60) and euthyroidism (n = 42). Antigen-specific enzyme-linked immunosorbent assay was used to detect the distribution of TPOAb IgG subclasses. The prevalence of TPOAb IgG subclasses in all patients' sera with HT was IgG1 70·2%, IgG2 35·1%, IgG3 19·6% and IgG4 66·1% respectively. The prevalence of IgG2 in sera from patients with hypothyroidism (51·5%) was significantly higher than that of subclinical hypothyroidism (33·3%) (P < 0·05), and the latter was also significantly higher than that of euthyroidism (11·9%) (P < 0·05). The positive percentage of IgG2 subclass in sera from patients with hypothyroidism and subclinical hypothyroidism was significantly higher than that of euthyroidism (P < 0·05), the prevalence and positive percentage of IgG4 subclass in sera from patients with hypothyroidism and subclinical hypothyroidism was significantly higher than that of euthyroidism respectively (P < 0·05). The predominant TPOAb IgG subclasses in sera from patients with HT were IgG1 and IgG4. Patients with high levels of TPOAb IgG2, IgG4 subclasses might be at high risk of developing overt hypothyroidism.

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Cytotoxic Assay of Circulating Thyroid Peroxidase Antibodies

Cited by 23 publications

References 22 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

Significance of thyroglobulin antibodies cross-reactive with thyroperoxidase (TGPO antibodies) in individual patients and immunized mice

Distribution of immunoglobulin G subclasses of anti-thyroid peroxidase antibody in sera from patients with Hashimoto's thyroiditis with different thyroid functional status

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