Busuttil B E, Frauman A G
Clinical Pharmacology and Therapeutics Unit, Department of Medicine, Austin and Repatriation Medical Center, University of Melbourne, Heidelberg, Victoria 3084, Australia.
J Clin Endocrinol Metab. 2001 May;86(5):2315-9. doi: 10.1210/jcem.86.5.7474.
The existence of an autoantigen common to Graves' disease and its associated extrathyroidal manifestations has been proposed. As the TSH receptor (TSHR) is the primary target for autoimmunity against the thyroid in Graves' disease, much effort has gone into investigating the role of TSHR messenger ribonucleic acid (mRNA) transcripts in extrathyroidal tissue, particularly in the orbit. A high stringency RT-PCR technique had previously been employed by our laboratory to demonstrate the presence of full-length and splice variant TSHR mRNA in extraocular muscle (EOM). This technique demonstrated selective amplification of TSHR mRNA transcripts in thyroid and EOM, but not in abdominal muscle, kidney, or brain tissue. We used this technique in the present study to investigate the reported presence of TSHR mRNA transcripts in cardiac tissue. After removal of all visible fat from muscle tissues, high stringency RT-PCR was performed, and we found no TSHR transcripts in the muscle of any chamber of the normal human heart. In addition, in situ hybridization on fresh-frozen and paraffin-embedded sections confirmed the presence of TSHR transcripts in thyroid and EOM, but not in abdominal or cardiac muscle. These findings support the hypothesis that the TSHR is a shared antigen in the thyroid and EOM, but not in cardiac muscle.
有人提出，格雷夫斯病及其相关的甲状腺外表现存在共同的自身抗原。由于促甲状腺激素受体（TSHR）是格雷夫斯病中针对甲状腺自身免疫的主要靶点，人们投入了大量精力来研究TSHR信使核糖核酸（mRNA）转录本在甲状腺外组织，尤其是眼眶中的作用。我们实验室先前采用了一种高严谨度的逆转录聚合酶链反应（RT-PCR）技术，以证明眼外肌（EOM）中存在全长和剪接变体TSHR mRNA。该技术证明了TSHR mRNA转录本在甲状腺和EOM中选择性扩增，但在腹肌、肾脏或脑组织中未扩增。在本研究中，我们使用该技术来调查心脏组织中是否存在报道的TSHR mRNA转录本。在从肌肉组织中去除所有可见脂肪后，进行了高严谨度RT-PCR，我们在正常人心脏任何腔室的肌肉中均未发现TSHR转录本。此外，对新鲜冷冻和石蜡包埋切片进行的原位杂交证实了TSHR转录本在甲状腺和EOM中存在，但在腹肌或心肌中不存在。这些发现支持了以下假设：TSHR是甲状腺和EOM中的共同抗原，但不是心肌中的共同抗原。
