Schuppert F, Taniguchi S, Schröder S, Dralle H, von zur Mühlen A, Kohn L D
Department of Clinical Endocrinology, Hannover Medical School, Germany.
J Clin Endocrinol Metab. 1996 Oct;81(10):3622-8. doi: 10.1210/jcem.81.10.8855812.
Increases in thyroid cell major histocompatibility complex (MHC) class I and class II expression have been suggested to be an important factor in the development or perpetuation of Graves' disease. It is hypothesized that elevations result in abnormal presentation of thyroid antigens to immune cells, and that iodide and/or methimazole (MMI) are effective therapeutic agents because, at least in part, of their suppression of MHC expression. In this report, we show that Graves' patients pretreated with iodide only 4 days before surgery have lower levels of MHC class I and class II RNA levels in their thyroid tissue than do patients with no iodide pretreatment (P < 0.001 and 0.03, respectively). Because patients in both groups are treated with MMI and because the change is independent of the amounts of MMI used to treat patients, the class I and class II changes cannot be ascribed to MMI. The iodide action to decrease MHC class I and class II RNA levels was duplicated using cultured human thyroid cells in vitro; the iodide effect was dependent on the iodide concentration, was not duplicated by chloride, was not associated with an alteration in cAMP levels or with a change in thyrotropin receptor RNA levels, and was evident in gamma-interferon-treated cells. The data suggest, therefore, that the therapeutic action of iodide in Graves' patients is associated with decreased MHC gene expression, that this action is a direct effect of high concentrations of iodide on the thyroid cells, and that altered MHC gene expression in the target tissue may well be associated with the development or perpetuation of Graves' disease.
甲状腺细胞主要组织相容性复合体（MHC）I类和II类表达的增加被认为是格雷夫斯病发生或持续存在的一个重要因素。据推测，这种升高会导致甲状腺抗原向免疫细胞的异常呈递，并且碘化物和/或甲巯咪唑（MMI）是有效的治疗药物，因为至少部分是由于它们对MHC表达的抑制作用。在本报告中，我们表明，仅在手术前4天用碘化物预处理的格雷夫斯病患者，其甲状腺组织中MHC I类和II类RNA水平低于未用碘化物预处理的患者（分别为P < 0.001和0.03）。由于两组患者均接受MMI治疗，且这种变化与用于治疗患者的MMI量无关，所以I类和II类的变化不能归因于MMI。在体外培养的人甲状腺细胞中重复了碘化物降低MHC I类和II类RNA水平的作用；碘化物的作用取决于碘化物浓度，氯化物不能重复该作用，与cAMP水平的改变或促甲状腺激素受体RNA水平的变化无关，并且在γ干扰素处理的细胞中也很明显。因此，数据表明，碘化物在格雷夫斯病患者中的治疗作用与MHC基因表达降低有关，这种作用是高浓度碘化物对甲状腺细胞的直接作用，并且靶组织中MHC基因表达的改变很可能与格雷夫斯病的发生或持续存在有关。
