生物技术单克隆抗体和受体拮抗剂能够针对特定的炎症因子，如细胞因子、细胞因子受体、共刺激分子或白细胞种群，成为治疗免疫病理学所致全身性炎症疾病的替代疗法。然而，免疫治疗也有可能增加全身性和器官特异性免疫介导疾病的发生率，尽管不是特别高，却也不可忽视。现在越来越明显的是，干扰一个特定的免疫途径可能有利于激活对抗性的补偿信号，这可能会加重潜在的亚临床疾病或导致与潜在疾病完全不同的免疫介导疾病。这种“补偿性免疫开关”主要出现在接受肿瘤坏死因子（TNF）-α抑制剂治疗的患者中，这是第一个获得批准治疗免疫病理学所致全身性炎症疾病的生物药物。在本综述中，我们描述了主要与TNF-α抑制剂相关的免疫介导疾病的临床特征和易感因素，并将它们组织成亚临床血清自身免疫、除了TNF-α抑制剂适应症外的自身免疫性疾病和矛盾反应等不同类型。我们还讨论了潜在的发病机制和治疗管理的注意事项。更好地理解TNF-α抑制剂和其他生物药物可能触发的“补偿性免疫开关”这一复杂现象，不仅有助于适当管理免疫介导疾病，还能更好地解释某些慢性炎症疾病的病因机制的异质性，尽管它们彼此不同，但被随意地归为过度通用的疾病分类单元。版权所有 © 2023。由Elsevier B.V.发布。

Biotechnological monoclonal antibodies and receptor antagonists capable of targeting specific inflammatory actors, such as cytokines, cytokines receptors, co-stimulatory molecules or leukocyte populations, have emerged as an alternative to conventional therapies for treating systemic inflammatory diseases with immune pathogenesis. However, there is no doubt that, with a frequency that is not exceptionally high but also not negligible, immunotherapies can favour the development of systemic and organ-specific immune-mediated disorders. It has become increasingly evident that interference with a specific immune pathway may favour the activation of opposing compensatory signalling, which may exacerbate underlying subclinical disorders or cause immune-mediated diseases completely different from the underlying disease. The 'compensatory immunological switch' has emerged primarily in patients treated with tumor necrosis factor (TNF) -α inhibitors, the first biological drugs approved for treating systemic inflammatory diseases with immune pathogenesis. In this Review, we describe the clinical features and predisposing factors of the main TNF-α inhibitor-related immune disorders, organising them into subclinical serological autoimmunity, autoimmune disorders other than those for which TNF-α inhibitors are indicated, and paradoxical reactions. We also discuss the underlying pathogenetic mechanisms and precautions for use in the therapeutic management of these patients. Better understanding of the complex phenomenon of the 'compensatory immunological switch', which TNF-α inhibitors and other biological drugs might trigger, can help not only appropriately managing immune-mediated disorders, but also better interpreting the heterogeneity of the pathogenetic mechanisms underlying certain chronic inflammatory conditions that, although different from each other, are arbitrarily placed in the context of overly generic nosological entities.Copyright © 2023. Published by Elsevier B.V.