Unit of Endocrinology, Department of Medicine and Sciences of Aging, University "G. D'Annunzio" and Aging Research Center, Centro Scienze dell'Invecchiamento, "Gabriele D'Annunzio" University Foundation, 66013 Chieti-Pescara, Italy.
J Clin Endocrinol Metab. 2012 Jul;97(7):E1106-15. doi: 10.1210/jc.2011-2893. Epub 2012 Apr 10.
Stimulating thyrotropin receptor (TSHr) autoantibodies (TSAb) are the cause of hyperthyroidism in Graves' disease. In a patient's serum, TSAb can coexist with antagonist TSHr autoantibodies that block TSAb stimulatory activity (TSBAb); both can vary in amount and time.
The objective of the study was to create a functional assay that detects only TSAb, thus having an increased accuracy for diagnosing Graves' disease.
A TSHr chimera (Mc4) that retains an agonist-sensitive TSAb epitope but replaces a TSBAb epitope was stably transfected in cells to establish the Mc4 assay.
The study was conducted at the Chieti University (Outpatient Endocrine Clinic) and the University of Pisa (the Department of Endocrinology).
The assay was validated using sera from 170 individuals with Graves' disease, Hashimoto's thyroiditis, and nonautoimmune hyperthyroidism and normal subjects from Chieti University. A second blinded study evaluated sera from 175 patients with autoimmune thyroid disease (mainly Graves' disease) from the University of Pisa.
Interventions included the assessment of patients' sera using human wild-type TSHr (WT-TSHr), Mc4 chimera, and binding (TRAb) assays.
The Mc4 assay has the best accuracy for diagnosing Graves' disease.
The Mc4 assay has a better diagnostic accuracy than WT-TSHr and second-generation TRAb assays. Indeed, the sensitivity of the WT-TSHr, TRAb, and Mc4 assays was 97.3, 86.5, and 100%, respectively, whereas the specificity was 93.1, 97, and 98.5%, respectively.
The Mc4 assay is a functional assay with improved sensitivity and specificity for the detection of TSAb and is clinically useful in diagnosing Graves' disease.
刺激促甲状腺激素受体（TSHr）自身抗体（TSAb）是格雷夫斯病发生甲状腺功能亢进的原因。在患者血清中，TSAb 可与阻断 TSAb 刺激活性的拮抗性 TSHr 自身抗体（TSBAb）共存；两者的数量和时间都可能有所不同。
本研究旨在创建一种仅检测 TSAb 的功能性测定法，从而提高诊断格雷夫斯病的准确性。
通过稳定转染 Mc4 嵌合体（Mc4）建立 Mc4 测定法，该嵌合体保留了激动剂敏感的 TSAb 表位，但替换了 TSBAb 表位。
本研究在切塞纳大学（门诊内分泌科）和比萨大学（内分泌科）进行。
使用来自切塞纳大学的 170 例格雷夫斯病、桥本甲状腺炎和非自身免疫性甲状腺功能亢进症以及正常个体的血清对该测定法进行了验证。第二项盲法研究评估了来自比萨大学的 175 例自身免疫性甲状腺疾病（主要为格雷夫斯病）患者的血清。
包括使用人野生型 TSHr（WT-TSHr）、Mc4 嵌合体和结合（TRAb）测定法评估患者的血清。
Mc4 测定法在诊断格雷夫斯病方面具有最佳的准确性。
Mc4 测定法比 WT-TSHr 和第二代 TRAb 测定法具有更好的诊断准确性。实际上，WT-TSHr、TRAb 和 Mc4 测定法的敏感性分别为 97.3%、86.5%和 100%，而特异性分别为 93.1%、97%和 98.5%。
Mc4 测定法是一种具有改善的敏感性和特异性的功能性测定法，用于检测 TSAb，在诊断格雷夫斯病方面具有临床应用价值。
