Winand R J, Anaraki F, Etienne-Decerf J, Galili U
Division of Thyroid Diseases, University of Liege, Sart-Tilman par Liege, Belgium.
J Immunol. 1993 Oct 1;151(7):3923-34.
Anti-Gal is a natural polyclonal antibody that constitutes 1% of circulating IgG in all humans and that interacts specifically with the mammalian carbohydrate epitope Gal alpha 1-3Gal beta 1-4GlcNAc-R (termed the alpha-galactosyl epitope). This epitope is abundant on thyrocytes, as well as, on other cells of nonprimate mammals, prosimians and New World monkeys, but its expression is diminished in Old World monkey, ape, and human tissues. We hypothesized that anti-Gal may bind in vitro to alpha-galactosyl epitopes on xenogeneic TSH receptors (TSHR) and mimic the effect of TSH on xenogeneic thyrocytes. Assays performed with porcine thyrocytes have indicated that anti-Gal can mimic in vitro TSH effects in stimulation for cAMP synthesis, 125I uptake, and cell proliferation. Furthermore, depletion of anti-Gal from serum of patients with Graves' disease resulted in elimination of a large proportion of the thyroid stimulating immunoglobulin activity and half of the thyroglobulin binding inhibiting Ig activity, when the sera were assayed with porcine thyrocytes. The effect of anti-Gal binding to alpha-galactosyl epitopes on TSHR was further demonstrated by the antibody-mediated stimulation for cAMP synthesis in mouse 3T3 cells (cells expressing alpha-galactosyl epitopes), which were transfected with recombinant human TSHR. CHO cells (cells lacking alpha-galactosyl epitopes), transfected with recombinant human TSHR were not stimulated by anti-Gal. It is, therefore, suggested that in studies on antibodies in Graves' disease sera, the effect of anti-Gal may be excluded by using target cells that are devoid of alpha-galactosyl epitopes. Alternatively, anti-Gal could be removed from the tested sera, before the assay with xenogeneic thyrocytes.
抗半乳糖（Anti-Gal）是一种天然多克隆抗体，在所有人的循环免疫球蛋白G（IgG）中占1%，它能与哺乳动物碳水化合物表位Galα1-3Galβ1-4GlcNAc-R（称为α-半乳糖基表位）特异性相互作用。该表位在甲状腺细胞以及非灵长类哺乳动物、原猴亚目动物和新大陆猴的其他细胞中大量存在，但在旧大陆猴、猿和人类组织中的表达减少。我们推测抗半乳糖可能在体外与异种促甲状腺激素受体（TSHR）上的α-半乳糖基表位结合，并模拟促甲状腺激素对异种甲状腺细胞的作用。用猪甲状腺细胞进行的实验表明，抗半乳糖在体外可模拟促甲状腺激素对环磷酸腺苷（cAMP）合成、碘摄取和细胞增殖的刺激作用。此外，用猪甲状腺细胞检测时，格雷夫斯病患者血清中抗半乳糖的去除导致大部分甲状腺刺激免疫球蛋白活性和一半的甲状腺球蛋白结合抑制Ig活性消失。抗半乳糖与TSHR上的α-半乳糖基表位结合的作用通过抗体介导的对转染了重组人TSHR的小鼠3T3细胞（表达α-半乳糖基表位的细胞）中cAMP合成的刺激进一步得到证实。转染了重组人TSHR的中国仓鼠卵巢（CHO）细胞（缺乏α-半乳糖基表位的细胞）不受抗半乳糖的刺激。因此，建议在研究格雷夫斯病血清中的抗体时，可通过使用缺乏α-半乳糖基表位的靶细胞来排除抗半乳糖的作用。或者，在用异种甲状腺细胞检测之前，可从检测血清中去除抗半乳糖。
