Saller B, Hörmann R, Mann K
Department of Internal Medicine II, Klinikum Grosshadem, University of Munich, Germany.
J Clin Endocrinol Metab. 1991 Jan;72(1):188-95. doi: 10.1210/jcem-72-1-188.
The close relationship between thyroid microsomal antigen and thyroid peroxidase (TPO) is now well established. The present study evaluates the significance of autoantibodies against TPO (anti-TPO-Abs) in the various forms and stages of autoimmune thyroid disease with respect to a possible heterogeneous nature and particularly to their influence on TPO activity. When measured by a RIA using purified human TPO, anti-TPO-Abs were highly correlated with microsomal antibodies determined by enyzme-linked immunosorbant assay (r = 0.96; P less than 0.0001) and with the results of a TPO immunoprecipitation assay using crude microsomal preparations (r = 0.76; P less than 0.001). Relating the results of these assays to the reactivities of patients' sera with thyroid microsomes in immunoblot under nonreducing and reducing conditions, discordant results could be observed in a few cases. Further analysis of these data indicate a heterogeneous nature of anti-TPO-Abs, which react with at least two antigenic domains of the TPO molecule. The comparative analysis of patients with hyperthyroid Graves' disease, patients with Graves' disease in clinical remission, and patients with hypothyroid Hashimoto's thyroiditis revealed no significant differences in the antibody spectrum. When evaluating the direct influence of anti-TPO-Abs on the activity of TPO under a rigorous methodological approach, we found no significant inhibition of the enzymatic activity by any of the sera investigated from patients with autoimmune thyroid disease compared to that in sera from normal controls. In conclusion, the data indicate a heterogeneous nature of anti-TPO-Abs. The spectrum of antigenic epitopes recognized by anti-TPO-Abs seems not to be significantly different in the various forms and stages of autoimmune thyroid disease. The lack of an inhibitory effect of autoantibodies on TPO activity argues against direct binding of autoantibodies to the enzymatic sites of TPO and indicates that they are not important factors in producing thyroid dysfunction in autoimmune thyroid disease.
甲状腺微粒体抗原与甲状腺过氧化物酶（TPO）之间的密切关系现已得到充分证实。本研究评估了针对TPO的自身抗体（抗TPO抗体）在自身免疫性甲状腺疾病的各种形式和阶段中的意义，涉及可能的异质性，特别是它们对TPO活性的影响。当使用纯化的人TPO通过放射免疫分析（RIA）进行测量时，抗TPO抗体与通过酶联免疫吸附测定法测定的微粒体抗体高度相关（r = 0.96；P小于0.0001），并且与使用粗微粒体制剂的TPO免疫沉淀测定结果相关（r = 0.76；P小于0.001）。将这些测定结果与患者血清在非还原和还原条件下在免疫印迹中与甲状腺微粒体的反应性相关联，在少数情况下可观察到不一致的结果。对这些数据的进一步分析表明抗TPO抗体具有异质性，它们与TPO分子的至少两个抗原结构域发生反应。对甲状腺功能亢进的格雷夫斯病患者、临床缓解期的格雷夫斯病患者和甲状腺功能减退的桥本甲状腺炎患者的比较分析显示，抗体谱没有显著差异。当在严格的方法学方法下评估抗TPO抗体对TPO活性的直接影响时我们发现，与正常对照血清相比，自身免疫性甲状腺疾病患者的任何研究血清均未对酶活性产生显著抑制。总之，数据表明抗TPO抗体具有异质性。在自身免疫性甲状腺疾病的各种形式和阶段中，抗TPO抗体识别的抗原表位谱似乎没有显著差异。自身抗体对TPO活性缺乏抑制作用，这与自身抗体直接结合到TPO的酶位点相矛盾，并表明它们不是自身免疫性甲状腺疾病中导致甲状腺功能障碍的重要因素。
