Estienne V, McIntosh R S, Ruf J, Asghar M S, Watson P F, Carayon P, Weetman A P
U38 INSERM, Faculté de Médecine, Université de la Méditerranée, Marseille, France.
Thyroid. 1998 Aug;8(8):643-6. doi: 10.1089/thy.1998.8.643.
Antibodies (Ab) to thyroglobulin (Tg) are common in patients with autoimmune thyroid diseases, but it is currently unclear how Tg Ab are involved in the pathology of autoimmune thyroid disease. We have previously reported the isolation of immunoglobulin G (IgG)kappa and IgGlambda Fab from phage display combinatorial libraries from the cervical lymph node of a single Hashimoto's thyroiditis patient with a high anti-Tg titer. Sequence analysis of these Fab indicated a restricted heavy chain usage with a nonrestricted light chain usage, with Fab inhibiting the binding of patient Tg Ab by between 39% and 79%. Comparative mapping of nine each of these IgGkappa and IgGlambda Fab, and the patient serum from whom the Fab were derived, is described here, using a panel of 10 murine monoclonal antibodies (Mab) to human thyroglobulin (hTg). The Fab interacted principally with mAb defining the overlapping antigenic domains I and IV, previously characterized as the region recognized by the majority of patient serum Tg Ab. Tg Ab from serum of the patient from whom the Fab were derived were also directed at this region, suggesting that the Fab are representative of the Tg Ab present in this patient.
甲状腺球蛋白（Tg）抗体（Ab）在自身免疫性甲状腺疾病患者中很常见，但目前尚不清楚Tg Ab如何参与自身免疫性甲状腺疾病的病理过程。我们之前报道过从一名抗Tg滴度高的桥本甲状腺炎患者的颈部淋巴结噬菌体展示组合文库中分离出免疫球蛋白G（IgG）κ和IgGλ Fab。这些Fab的序列分析表明重链使用受限而轻链使用不受限，Fab对患者Tg Ab结合的抑制率在39%至79%之间。本文使用一组针对人甲状腺球蛋白（hTg）的10种鼠单克隆抗体（Mab），描述了这些IgGκ和IgGλ Fab各9个以及产生这些Fab的患者血清的比较图谱。这些Fab主要与定义重叠抗原结构域I和IV的单克隆抗体相互作用，之前已将该区域鉴定为大多数患者血清Tg Ab识别的区域。来自产生这些Fab的患者血清中的Tg Ab也针对该区域，这表明这些Fab代表了该患者体内存在的Tg Ab。
