Winand R J, Devigne J W, Meurisse M, Galili U
Division of Thyroid Diseases, University of Liege, Sart-Tilman Par Liege, Belgium.
J Immunol. 1994 Aug 1;153(3):1386-95.
Anti-Gal is a natural Ab abundantly produced in humans. It interacts specifically with the carbohydrate epitope Gal alpha 1-3Gal beta 1-4GlcNAc-R (termed the alpha-galactosyl epitope). This epitope is expressed in large amounts on thyrocytes of nonprimate mammals, but not of humans. We have previously found that binding of anti-Gal to alpha-galactosyl epitopes on porcine thyrocytes results in stimulatory effects similar to those exerted by thyroid-stimulating hormone (thyrotropin). In the present study, we tested the hypothesis that anti-Gal may contribute to Graves' disease (GD) pathogenesis by stimulation of the thyrocytes of patients with this autoimmune disorder. Anti-Gal binding and stimulatory effects were assessed in primary thyrocyte cultures. Anti-Gal specifically bound to GD thyrocytes and induced an increase in cAMP synthesis, 125I uptake, and DNA synthesis in these cells. Furthermore, the stimulatory effects of autologous sera on GD thyrocytes were greatly reduced after specific depletion of anti-Gal from these sera. No binding and no stimulatory effects of anti-Gal were observed, however, with normal human thyrocytes and with thyrocytes from thyrotoxic patients who lack thyroid-stimulating Igs or thyrotropin binding inhibiting Igs. These in vitro stimulatory effects of anti-Gal on GD thyrocytes suggest that this natural Ab may contribute to the in vivo continuous stimulation of thyrocytes in GD patients. The possibility that anti-Gal may stimulate GD thyrocytes via interaction with aberrantly expressed alpha-galactosyl epitopes on the thyroid-stimulating hormone receptor is discussed.
抗半乳糖抗体（Anti-Gal）是人体大量产生的一种天然抗体。它特异性地与碳水化合物表位半乳糖α1-3半乳糖β1-4N-乙酰葡糖胺-R（称为α-半乳糖基表位）相互作用。这种表位在非灵长类哺乳动物的甲状腺细胞中大量表达，但在人类甲状腺细胞中不表达。我们之前发现，抗半乳糖抗体与猪甲状腺细胞上的α-半乳糖基表位结合会产生类似于促甲状腺激素（促甲状腺素）所产生的刺激作用。在本研究中，我们检验了这样一个假说，即抗半乳糖抗体可能通过刺激患有这种自身免疫性疾病患者的甲状腺细胞而促成格雷夫斯病（GD）的发病机制。在原代甲状腺细胞培养物中评估了抗半乳糖抗体的结合和刺激作用。抗半乳糖抗体特异性地结合GD甲状腺细胞，并诱导这些细胞中cAMP合成增加、125I摄取增加和DNA合成增加。此外，从这些血清中特异性去除抗半乳糖抗体后，自体血清对GD甲状腺细胞的刺激作用大大降低。然而，在正常人甲状腺细胞以及缺乏甲状腺刺激免疫球蛋白或促甲状腺素结合抑制免疫球蛋白的甲状腺毒症患者的甲状腺细胞中，未观察到抗半乳糖抗体的结合和刺激作用。抗半乳糖抗体对GD甲状腺细胞的这些体外刺激作用表明，这种天然抗体可能在体内促成对GD患者甲状腺细胞的持续刺激。文中还讨论了抗半乳糖抗体可能通过与促甲状腺激素受体上异常表达的α-半乳糖基表位相互作用来刺激GD甲状腺细胞的可能性。
