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利用猪甲状腺细胞评估自身免疫性甲状腺疾病中的抗体依赖性细胞毒性。

Assessment of antibody dependent cell cytotoxicity in autoimmune thyroid disease using porcine thyroid cells.

作者信息

Rodien P, Madec A M, Morel Y, Stefanutti A, Bornet H, Orgiazzi J

机构信息

INSERM U. 197, Faculté de Medecine Alexis Carrel, Lyon, France.

出版信息

Autoimmunity. 1992;13(3):177-85. doi: 10.3109/08916939209004822.

Abstract

Antibody Dependent Cell Cytotoxicity (ADCC) appears to be involved in Autoimmune Thyroid Disease (AITD). Homologous system may trigger non-specific reactions which might obscure specific ADCC. Heterologous target cells may be useful for studying ADCC, provided relevant antigen(s) are expressed. We therefore tested the capacity of porcine thyroid cells to elicit ADCC reaction in the presence of sera from various patients with AITD. Porcine thyroid cells were used in a 4-hr chromium release assay in the presence of 1/10 heat inactivated human sera and human peripheral blood lymphocytes at a 30:1 effector-target ratio. There was a significant correlation (r = 0.64; P < 0.01) between ADCC activities tested on human or porcine thyroid cells. Serum or IgG effects on porcine thyroid ADCC were dose-dependent between 1/10 to 1/10,000 dilutions. Non-thyroid cell systems were unaffected by thyroid cytotoxic sera. Porcine thyrocyte susceptibility to ADCC peaked at the fourth day of culture and was enhanced by addition of TSH or TSH and methimazole in the culture medium. Using this heterologous system, we demonstrated ADCC activity in a significant proportion of patients with thyroiditis (14/19), Graves' opthalmopathy (19/44) or of mothers of children with congenital hypothyroidism (14/39) and in the children themselves (15/39). Discrepancies observed in some sera between ADCC activity and antithyroperoxidase antibody suggest that thyroperoxidase is not the only antigen involved in ADCC. These results indicate that porcine thyroid cells appear suitable for ADCC assay in patients with AITD. Also this system should be helpful to characterize the antigen-antibody involved.

摘要

抗体依赖细胞介导的细胞毒性作用(ADCC)似乎与自身免疫性甲状腺疾病(AITD)有关。同源系统可能引发非特异性反应,这可能会掩盖特异性ADCC。如果表达了相关抗原,异源靶细胞可能有助于研究ADCC。因此,我们测试了猪甲状腺细胞在存在各种AITD患者血清的情况下引发ADCC反应的能力。在30:1的效应细胞与靶细胞比例下,将猪甲状腺细胞用于4小时的铬释放试验,同时加入1/10热灭活的人血清和人外周血淋巴细胞。在人或猪甲状腺细胞上测试的ADCC活性之间存在显著相关性(r = 0.64;P < 0.01)。血清或IgG对猪甲状腺ADCC的影响在1/10至1/10,000稀释度之间呈剂量依赖性。非甲状腺细胞系统不受甲状腺细胞毒性血清的影响。猪甲状腺细胞对ADCC的敏感性在培养的第四天达到峰值,并通过在培养基中添加促甲状腺激素(TSH)或TSH和甲巯咪唑而增强。使用这种异源系统,我们在很大比例的甲状腺炎患者(14/19)、格雷夫斯眼病患者(19/44)或先天性甲状腺功能减退症患儿的母亲(14/39)以及患儿自身(15/39)中证明了ADCC活性。在一些血清中观察到的ADCC活性与抗甲状腺过氧化物酶抗体之间的差异表明,甲状腺过氧化物酶不是参与ADCC的唯一抗原。这些结果表明,猪甲状腺细胞似乎适用于AITD患者的ADCC检测。此外,该系统应有助于鉴定所涉及的抗原-抗体。

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