Mariotti S, Caturegli P, Piccolo P, Barbesino G, Pinchera A
Istituto di Endocrinologia, Università di Pisa, Italy.
J Clin Endocrinol Metab. 1990 Sep;71(3):661-9. doi: 10.1210/jcem-71-3-661.
Thyroid microsomal antibodies (anti-M Ab) have been recently proven to be directed to thyroid peroxidase (TPO). Methods to detect anti-TPO antibodies (anti-TPO Ab) employing purified antigen have been developed, but the available information on the clinical usefulness of this technique is still limited to small patient series. In the present investigation anti-TPO Ab were assayed by a newly developed monoclonal antibody-assisted RIA in a large number (n = 715) of subjects, including 119 normal controls and 596 patients with different autoimmune or nonautoimmune thyroid disease: Anti-TPO Ab were detected in 10 of 119 (8.4%; range, 11-210 U/mL) normal controls, 134 of 181 (74%; range, 11-74.000 U/mL) patients with Graves' disease, all but 1 of 144 (99.3%; range, 11-90.000 U/mL) with Hashimoto's thyroiditis (n - 98) or idiopathic myxedema (n = 46), 20 of 180 (11.1%; range, 11-6.700 U/mL) with miscellaneous nonautoimmune thyroid diseases, 16 of 83 (19.2%; range, 11-6.600 U/mL) patients with differentiated thyroid carcinoma, and in none of 8 patients with subacute thyroiditis. The highest anti-TPO Ab concentrations were found in untreated hypothyroid Hashimoto's thyroiditis, but no simple relationship between anti-TPO Ab levels and thyroid function was observed. Anti-TPO Ab significantly decreased in patients with Graves' disease after treatment with methimazole and in those with hypothyroid Hashimoto's thyroiditis or idiopathic myxedema during L-T4 administration. A highly significant positive correlation (r = 0.979; P less than 0.001) was found between anti-M Ab titers by passive hemagglutination (PH; available in 650 sera) and the corresponding average anti-TPO Ab by RIA; discrepant results were almost exclusively limited to sera with negative or low (1:100-1:400) anti-M Ab titers. Analysis of these discrepant data indicated higher autoimmune disease specificity and sensitivity of anti-TPO Ab RIA tests compared to anti-M Ab by PH. Absorption studies showed that interference of anti-Tg Ab was responsible for anti-M Ab-positive tests in occasional anti-TPO Ab-negative/anti-M Ab-positive sera from autoimmune thyroid disease patients. Anti-TPO Ab determination by RIA was unaffected by circulating thyroglobulin concentrations up to more than 10,000 ng/mL. In conclusion, anti-TPO Ab assay by monoclonal antibody-assisted RIA appears to be more sensitive and specific for thyroid autoimmune diseases than anti-M Ab determination by PH. Since the assay is easy to perform and employs only tracer amounts of purified antigen, these characteristics should allow its rapid diffusion to the clinical routine.
甲状腺微粒体抗体（抗-M抗体）最近已被证实是针对甲状腺过氧化物酶（TPO）的。已开发出利用纯化抗原检测抗TPO抗体（抗-TPO Ab）的方法，但关于该技术临床应用价值的现有信息仍仅限于少量患者系列。在本研究中，采用新开发的单克隆抗体辅助放射免疫分析法（RIA）对大量（n = 715）受试者进行了抗-TPO Ab检测，其中包括119名正常对照和596例患有不同自身免疫性或非自身免疫性甲状腺疾病的患者：119名正常对照中有10名（8.4%；范围为11 - 210 U/mL）检测到抗-TPO Ab，181例格雷夫斯病患者中有134例（74%；范围为11 - 74,000 U/mL），144例桥本甲状腺炎（n = 98）或特发性黏液水肿（n = 46）患者中除1例（99.3%；范围为11 - 90,000 U/mL）外均检测到，180例其他非自身免疫性甲状腺疾病患者中有20例（11.1%；范围为11 - 6,700 U/mL），83例分化型甲状腺癌患者中有16例（19.2%；范围为11 - 6,600 U/mL），而8例亚急性甲状腺炎患者均未检测到。未经治疗的甲状腺功能减退桥本甲状腺炎患者中抗-TPO Ab浓度最高，但未观察到抗-TPO Ab水平与甲状腺功能之间存在简单关系。格雷夫斯病患者用甲巯咪唑治疗后以及甲状腺功能减退的桥本甲状腺炎或特发性黏液水肿患者在服用左甲状腺素（L-T4）期间，抗-TPO Ab显著降低。通过被动血凝试验（PH；650份血清可用）检测的抗-M抗体滴度与相应的RIA平均抗-TPO Ab之间发现高度显著的正相关（r = 0.979；P < 0.001）；不一致的结果几乎完全局限于抗-M抗体滴度为阴性或低（1:100 - 1:400）的血清。对这些不一致数据的分析表明，与通过PH检测抗-M抗体相比，抗-TPO Ab RIA检测对自身免疫性疾病具有更高的特异性和敏感性。吸收研究表明，抗-Tg抗体的干扰是自身免疫性甲状腺疾病患者偶尔出现的抗-TPO Ab阴性/抗-M Ab阳性血清中抗-M抗体阳性检测结果的原因。RIA法检测抗-TPO Ab不受循环甲状腺球蛋白浓度高达10,000 ng/mL以上的影响。总之，单克隆抗体辅助RIA法检测抗-TPO Ab似乎比PH法检测抗-M抗体对甲状腺自身免疫性疾病更敏感、更特异。由于该检测方法易于操作且仅使用痕量的纯化抗原，这些特性应使其能够迅速推广应用于临床常规检测。
