Endo T, Kaneshige M, Nakazato M, Kogai T, Saito T, Onaya T
Third Department of Internal Medicine, Yamanashi Medical University, Japan.
Biochem Biophys Res Commun. 1996 Nov 1;228(1):199-202. doi: 10.1006/bbrc.1996.1639.
Recently we have newly identified an autoantibody against thyroid iodide transporter (TIT) in the sera from patients with autoimmune thyroid disease. In order to study the function of these autoantibodies, we established CHO-KI cells stably expressing recombinant rat TIT (CHO-TIT cells), and the effect of IgGs from the patients with Hashimoto's thyroiditis on iodide uptake activity of CHO-TIT cells was investigated. We found that 4 out of 34 sera from patients with Hashimoto's thyroiditis strongly recognized TIT by Western blot analysis. These 4 IgGs, purified by protein A column chromatography, caused 14 to 62% inhibition of I- accumulation in CHO-TIT cells. Next, using synthetic peptides, we determined the recognition site of the autoantibody on the TIT molecule. The autoantibody reacted with the synthetic peptide corresponding to the 6th extracellular loop of the TIT molecule. These results suggest that autoantibody against TIT in the sera from patients with Hashimoto's thyroiditis binds to the 6th extracellular loop of TIT protein and inhibits I- transport into the thyrocytes. Anti-TIT autoantibody might participate in the pathogenesis of Hashimoto's thyroiditis and modulate thyroid function of patients with the disease.
最近，我们在自身免疫性甲状腺疾病患者的血清中，新发现了一种针对甲状腺碘转运体（TIT）的自身抗体。为了研究这些自身抗体的功能，我们构建了稳定表达重组大鼠TIT的CHO-KI细胞（CHO-TIT细胞），并研究了桥本甲状腺炎患者的IgG对CHO-TIT细胞碘摄取活性的影响。通过蛋白质印迹分析，我们发现34例桥本甲状腺炎患者血清中有4例能强烈识别TIT。通过蛋白A柱层析纯化得到的这4种IgG，可使CHO-TIT细胞中的碘积累受到14%至62%的抑制。接下来，我们利用合成肽确定了自身抗体在TIT分子上的识别位点。该自身抗体与对应于TIT分子第6个细胞外环的合成肽发生反应。这些结果表明，桥本甲状腺炎患者血清中针对TIT的自身抗体与TIT蛋白的第6个细胞外环结合，并抑制碘转运进入甲状腺细胞。抗TIT自身抗体可能参与桥本甲状腺炎的发病机制，并调节该病患者的甲状腺功能。
