Rodien P, Madec A M, Ruf J, Rajas F, Bornet H, Carayon P, Orgiazzi J
INSERM U-449, Faculté de Médecine R. Laënnec, Lyon, France.
J Clin Endocrinol Metab. 1996 Jul;81(7):2595-600. doi: 10.1210/jcem.81.7.8675583.
Thyroid antibody-dependent cell-mediated cytotoxicity (ADCC) has been reported in autoimmune thyroid disease, and its relationship with antithyroperoxidase antibodies (TPOAb) questioned. We studied the effect of highly purified human thyroperoxidase (TPO) on thyroid ADCC activity elicited by serum from patients with autoimmune thyroid disease. ADCC promoted by a pool of Graves' disease sera could be inhibited by the addition of TPO in a dose-dependent manner. TPO at 40 micrograms/mL decreased the ADCC observed in the presence of this serum pool by 50%. In the presence of 40 micrograms/mL TPO, ADCC was significantly reduced (P < 0.0005) from 39.6 +/- 10.6% (mean +/- SD) to 14.0 +/- 12.9% for the 18 Graves' disease sera tested and from 39.1 +/- 10.5% to 6.1 +/- 1.7% for the 16 thyroiditis sera tested. Purified thyroglobulin had no effect. Immunoaffinity-purified TPOAb could mediate ADCC in a dose-dependent manner, whereas purified antithyroglobulin antibodies could not. Three TPOAb-positive, but ADCC-negative, sera appear to contain an activity able to protect thyroid cells from ADCC. This protective effect is also observed on human fibroblasts. In conclusion, TPO is the major antigen involved in thyroid ADCC.
甲状腺抗体依赖的细胞介导的细胞毒性作用（ADCC）已在自身免疫性甲状腺疾病中被报道，其与抗甲状腺过氧化物酶抗体（TPOAb）的关系受到质疑。我们研究了高度纯化的人甲状腺过氧化物酶（TPO）对自身免疫性甲状腺疾病患者血清引发的甲状腺ADCC活性的影响。格雷夫斯病血清池促进的ADCC可被添加TPO以剂量依赖的方式抑制。40微克/毫升的TPO使在该血清池存在下观察到的ADCC降低了50%。在存在40微克/毫升TPO的情况下，对于所检测的18份格雷夫斯病血清，ADCC从39.6±10.6%（平均值±标准差）显著降低（P<0.0005）至14.0±12.9%，对于所检测的16份甲状腺炎血清，ADCC从39.1±10.5%降至6.1±1.7%。纯化的甲状腺球蛋白没有作用。免疫亲和纯化的TPOAb可呈剂量依赖地介导ADCC，而纯化的抗甲状腺球蛋白抗体则不能。三份TPOAb阳性但ADCC阴性的血清似乎含有一种能够保护甲状腺细胞免受ADCC作用的活性。在人成纤维细胞上也观察到这种保护作用。总之，TPO是参与甲状腺ADCC的主要抗原。
