EVIDENCE FOR IGG AUTOANTIBODIES TO GALECTIN-3, A BETA-GALACTOSIDE-BINDING LECTIN (MAC-2, EPSILON-BINDING-PROTEIN, OR CARBOHYDRATE-BINDING PROTEIN-35) IN HUMAN SERUM
EVIDENCE FOR IGG AUTOANTIBODIES TO GALECTIN-3, A BETA-GALACTOSIDE-BINDING LECTIN (MAC-2, EPSILON-BINDING-PROTEIN, OR CARBOHYDRATE-BINDING PROTEIN-35) IN HUMAN SERUM
复制标题
DOI：
10.1007/bf01541323
复制
发表时间：
1995-11-01
影响因子：
9.1
通讯作者：
LIU, FT
中科院分区：
文献类型：
--
作者：
MATHEWS, KP;KONSTANTINOV, KN;LIU, FT
半乳糖凝集素-3是一种β-半乳糖苷结合的动物凝集素，以前称为β-半乳糖苷结合蛋白、Mac-2、碳水化合物结合蛋白35、CBH 30、L-29或L34。研究了半乳糖凝集素-3自身抗体的可能发生，因为半乳糖凝集素与IgE或Fc β RI结合的交联可能产生肥大细胞或嗜碱性粒细胞释放的介质。出乎意料的是，通过ELISA，使用半乳糖凝集素-3包被的威尔斯孔与测试血清孵育，然后与HRPO缀合的山羊抗人IgG孵育，发现来自无当前过敏症状的个体的对照血清具有显著升高的IgG抗半乳糖凝集素-3水平。该反应不可由乳糖引起，表明其不是IgG通过凝集素-碳水化合物相互作用与半乳糖凝集素-3结合的结果。抗体活性被半乳糖凝集素-3和A蛋白偶联的琼脂糖凝胶特异性吸附，主要与IgG 1亚类相关。通过显示IgG与30-kD半乳糖凝集素-3条带结合的免疫印迹证实抗体的存在。相关表位位于galectin-3的N端结构域。先证者随后被发现患有结肠腺癌;并且发现IgG抗半乳糖凝集素-3的滴度在半结肠切除术后急剧升高。在家庭成员中尚未发现类似的抗体滴度，但已发现少数正常人和恶性肿瘤患者存在IgG抗半乳凝素-3抗体滴度低于先证者的证据。这种自身免疫反应的发病机制尚不清楚，但有一种趋势，它发生在老年人。
Galectin-3 is a beta-galactoside-binding animal lectin formerly called epsilon binding protein, Mac-2, carbohydrate binding protein 35, CBH 30, L-29, or L34. The possible occurrence of autoantibodies to galectin-3 was investigated because crosslinking of galectins bound to IgE or Fc epsilon RI might produce mediator release from mast cells or basophils. Unexpectedly, a control serum from an individual free of current allergic symptoms was found to have a significantly elevated level of IgG anti-galectin-3 by ELISA employing galectin-3-coated wells incubated with test serum followed by HRPO-conjugated goat anti-human IgG. The reaction was not inhibitable by lactose, suggesting that it is not a result of binding of IgG by galectin-3 through lectin-carbohydrate interactions. The antibody activity was specifically adsorbed by galectin-3 and protein A-conjugated Sepharose and was associated primarily with subclass IgG1. The presence of the antibodies was confirmed by immunoblotting showing binding of IgG to the 30-kD galectin-3 band. The relevant epitopes were in the galectin-3 N-terminal domain. The propositus was subsequently found to have adenocarcinoma of the colon; and titers of IgG anti-galectin-3 were found to be sharply elevated after hemicolectomy. Similar antibody titers have not been found iii family members, but small numbers of normal persons and patients with malignant neoplasms have been found to have evidence of IgG anti-galectin-3 antibodies at lower titers than the propositus. The pathogenesis of this autoimmune reaction is unclear, though there is a trend for it to occur in older persons.