Weetman A P, Black C M, Cohen S B, Tomlinson R, Banga J P, Reimer C B
Department of Medicine, University of Cambridge Clinical School, Addenbrooke's Hospital, UK.
Scand J Immunol. 1989 Jul;30(1):73-82. doi: 10.1111/j.1365-3083.1989.tb01190.x.
To delineate accurately the IgG subclass distribution of thyroid auto-antibodies, sera from nine patients with Hashimoto's thyroiditis were fractionated into IgG subclasses by complete depletion of the other IgG subclasses on affinity columns. All IgG subclass fractions contained thyroglobulin and microsomal (or thyroid peroxidase) antibody activity, although when compared to the total serum concentrations of IgG subclasses, IgG4 antibodies were overrepresented. However, in contrast to recent studies, this particular subclass never predominated--IgG4 antibody levels being exceeded by those of the IgG1 and IgG2 subclasses; it seems likely that these differences relate to varying sensitivity for different subclasses in previously used assay methods. This pattern of subclass activity differed from that of tetanus toxoid antibodies, which were found in six subjects. There was no light chain restriction within any subclass, showing that the overproduction of IgG4 thyroid antibodies is not of monoclonal origin. The functional affinity of subclasses for both thyroid antigens varied between patients, but IgG2 subclass fractions showed the highest functional affinity in the majority of samples. We also found that IgG2 subclass thyroid antibodies were ineffective in eliciting antibody-dependent cell-mediated cytotoxicity, as distinct from the other three subclasses. Our results show that thyroid antibodies are less restricted in their IgG subclass distribution and patients are less heterogeneous than previously described. Moreover, IgG2 thyroid antibodies are quantitatively important and differ in relative functional affinity and effector function from IgG1 and IgG4 thyroid antibodies.
为了准确描绘甲状腺自身抗体的IgG亚类分布情况，通过在亲和柱上完全去除其他IgG亚类，将9例桥本甲状腺炎患者的血清分离为IgG亚类。所有IgG亚类组分均含有甲状腺球蛋白和微粒体（或甲状腺过氧化物酶）抗体活性，尽管与IgG亚类的总血清浓度相比，IgG4抗体的含量过高。然而，与最近的研究不同，这个特定亚类从未占主导地位——IgG4抗体水平被IgG1和IgG2亚类超过；这些差异似乎与先前使用的检测方法中不同亚类的敏感性不同有关。这种亚类活性模式与在6名受试者中发现的破伤风类毒素抗体不同。任何亚类内均无轻链限制，表明IgG4甲状腺抗体的过度产生并非单克隆起源。不同患者的亚类对两种甲状腺抗原的功能亲和力各不相同，但在大多数样本中，IgG2亚类组分显示出最高的功能亲和力。我们还发现，与其他三个亚类不同，IgG2亚类甲状腺抗体在引发抗体依赖性细胞介导的细胞毒性方面无效。我们的结果表明，甲状腺抗体在IgG亚类分布上的限制较少，患者之间的异质性也比先前描述的要小。此外，IgG2甲状腺抗体在数量上很重要，并且在相对功能亲和力和效应功能方面与IgG1和IgG4甲状腺抗体不同。
