Immunoallergology Unit, University Hospital Careggi , Florence, Italy.
Translational Unit, Immunology Area, Pediatric Hospital Bambino Gesù, IRCCS , Rome, Italy.
Expert Rev Clin Pharmacol. 2021 Jan;14(1):47-53. doi: 10.1080/17512433.2020.1772053. Epub 2020 Jun 8.
Biological agents (BAs) target molecules involved in disease mechanisms and have modified the natural history of several immune-mediated disorders. All BAs are immunogenic, resulting in the formation of antidrug antibodies (ADAs), which can neutralize drug activity leading to loss of response and potential relapse, or serious adverse events such as infusion hypersensitivity reactions. The production of ADAs is the result of a specific adaptive immune response in which T and B cells are involved.
Factors conditioning the immunogenicity of BAs, including drug-, treatment- and patient-related factors are currently the subject of many studies. Among them, a lot of attention is dedicated to define the impact of BAs structure, the effect of targeting (soluble or membrane) molecules, the impact of interruption of therapy as well as the role of genetic (HLA and non-HLA) predisposing factors and disease activity.
Knowledge of factors capable of influencing the immunogenicity of BAs may help to understand, in a predictive manner and at the single patient level, the presence of risk factors influencing the production of ADAs and their impact on clinical outcomes.
生物制剂（BAs）针对疾病机制中涉及的分子，改变了几种免疫介导的疾病的自然病史。所有 BAs 都是免疫原性的，导致产生抗药物抗体（ADAs），这可能会中和药物的活性，导致应答丧失和潜在的复发，或严重的不良反应，如输注过敏反应。ADA 的产生是 T 和 B 细胞参与的特定适应性免疫反应的结果。
影响 BAs 免疫原性的因素，包括药物、治疗和患者相关因素，目前是许多研究的主题。其中，人们非常关注 BAs 结构、靶向（可溶性或膜）分子的影响、治疗中断的影响以及遗传（HLA 和非 HLA）易感因素和疾病活动的作用。
了解能够影响 BAs 免疫原性的因素，可能有助于在预测性和个体化患者水平上，了解影响 ADA 产生的风险因素及其对临床结果的影响。
