Zakarija M, De Forteza R, McKenzie J M, Ghandur-Mnaymneh L
Department of Medicine, University of Miami School of Medicine, FL 33101, USA.
Autoimmunity. 1994;19(1):31-7. doi: 10.3109/08916939409008006.
We reported a patient who gave birth to 3 children with transient neonatal hypothyroidism. She had 3 different antibodies (Ab) to the thyrotropin receptor (TSHR) in her serum, viz., TSH binding-inhibiting (TBIAb), thyroid-stimulating (TSAb) and an additional stimulating Ab (SAb). The SAb differed from TSAb in that its in vitro stimulating effect in human thyroid and FRTL5 cells was not inhibited by TBIAb [similar data now obtained with Chinese hamster ovary (CHO) cells transfected with cloned human TSHR]. Because of symptomatic goiter enlargement the patient underwent subtotal thyroidectomy. About 50% of the gland was infiltrated with lymphocytes; thyroid follicles had columnar epithelium, despite suppression of TSH by thyroxine and the presence of the potent TBIAb. Fifteen months later, when all 3 Ab showed a decline of approximately 3 fold, she gave birth to hypothyroid twins. These data support the following conclusions: 1) thyroidectomy and immunosuppression of pregnancy do not prevent neonatal thyroid disease if TSHR Ab (TRAb) are of high titer; 2) the thyroid is not a major site of TRAb production; 3) SAb is a thyroid stimulator, distinct from TSAb in that it does not share binding epitopes on the TSHR with either TSH or TBIAb; 4) SAb was the probable cause of thyroid growth in this patient.
我们报告了一位产下3名患有短暂性新生儿甲状腺功能减退症患儿的患者。她的血清中存在3种不同的促甲状腺激素受体（TSHR）抗体（Ab），即促甲状腺激素结合抑制性抗体（TBIAb）、促甲状腺素抗体（TSAb）和另一种刺激性抗体（SAb）。SAb与TSAb的不同之处在于，其在人甲状腺和FRTL5细胞中的体外刺激作用不受TBIAb抑制[目前用转染了克隆人TSHR的中国仓鼠卵巢（CHO）细胞也获得了类似数据]。由于出现有症状的甲状腺肿大，该患者接受了甲状腺次全切除术。约50%的腺体被淋巴细胞浸润；尽管甲状腺素抑制了促甲状腺激素且存在强效TBIAb，但甲状腺滤泡仍有柱状上皮。15个月后，当所有3种抗体均下降约3倍时，她产下了甲状腺功能减退的双胞胎。这些数据支持以下结论：1）如果TSHR抗体（TRAb）滴度高，甲状腺切除术和孕期免疫抑制并不能预防新生儿甲状腺疾病；2）甲状腺不是TRAb产生的主要部位；3）SAb是一种甲状腺刺激剂，与TSAb不同，它在TSHR上不与促甲状腺激素或TBIAb共享结合表位；4）SAb可能是该患者甲状腺生长的原因。
