Antibody formation to human(ized) therapeutic antibodies in humans is highly skewed toward anti-idiotype responses, probably because the idiotype is the only ‘foreign’ part of the antibody molecule. Here, we analyzed antibody responses to F(ab’)2 fragments of a panel of 17 human(ized) therapeutic antibodies in rabbits. Homology between the rabbit germline and the human(ized) antibodies is moderate not only for the variable domains (both the complementarity-determining regions and the framework regions), but also for the constant domains (66% or less). Nevertheless, we observed a highly skewed anti-idiotype response in all cases, with up to >90% of the antibodies directed toward the idiotype. These results indicate that the idiotype may be inherently immunodominant. We used these biased responses to raise monoclonal rabbit anti-idiotype antibodies against secukinumab, ustekinumab, reslizumab, mepolizumab, palivizumab, and dupilumab and demonstrate the potential to develop sensitive pharmacokinetic assays with these antibodies.

人体中针对人（化）治疗性抗体的抗体形成高度倾向于抗独特型应答，这可能是因为独特型是抗体分子的唯一“外来”部分。在这里，我们分析了兔中一组17种人源化治疗性抗体的F（ab'）2片段的抗体应答。兔种系和人源化抗体之间的同源性不仅对于可变域（互补决定区和框架区）均适中，对于恒定域（66％或更少）也适中。尽管如此，我们在所有情况下都观察到了高度偏斜的抗独特型反应，多达90％以上的抗体针对独特型。这些结果表明，独特型可能是固有的免疫优势。