Vultaggio Alessandra, Petroni Giulia, Pratesi Sara, Nencini Francesca, Cammelli Daniele, Ferraro Andrea, Maggi Enrico, Matucci Andrea
Centre of Excellence Denothe and Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
Department of Biomedicine, Immunoallergology Section, AOU Careggi, University of Florence, Florence, Italy.
J Int Med Res. 2016 Sep;44(1 suppl):38-42. doi: 10.1177/0300060515593248.
Biological agents target disease mechanisms and have modified the natural history of several immune-mediated disorders. Biological agents are structurally immunogenic, and therefore usually elicit a minor, subclinical and transient phenomenon. Occasionally, however, these drugs induce complete cellular and humoral immune responses, with the main clinical consequences being hypersensitivity reactions or loss of treatment response. This article considers the relative pathogenic mechanisms influencing immunogenicity in biological agents and discusses mechanisms of tolerance and adaptive immune response, including adaptive T-regulatory cell induction and immune response induction. Methods of determining cellular and humoral immune response to biological agents are identified and examined. Assays to detect antidrug antibodies and their isotypes can assist in monitoring immunogenicity and in preventing adverse events. Such strategies also enable resource conservation and may provide regulatory authorities with new insights that can be useful during the process of approving new biological or biosimilar agents.
生物制剂作用于疾病机制，改变了几种免疫介导疾病的自然病程。生物制剂在结构上具有免疫原性，因此通常会引发轻微、亚临床和短暂的现象。然而，这些药物偶尔会诱导完全的细胞免疫和体液免疫反应，主要临床后果是过敏反应或治疗反应丧失。本文探讨了影响生物制剂免疫原性的相关致病机制，并讨论了耐受性和适应性免疫反应的机制，包括适应性调节性T细胞诱导和免疫反应诱导。确定对生物制剂的细胞免疫和体液免疫反应的方法也得到了识别和研究。检测抗药抗体及其亚型的试验有助于监测免疫原性和预防不良事件。这些策略还能节约资源，并可能为监管机构提供新的见解，有助于在批准新的生物制剂或生物类似药的过程中发挥作用。
