Chemical- and Drug-Induced Allergic, Inflammatory, and Autoimmune Diseases Via Haptenation.
Chemical- and Drug-Induced Allergic, Inflammatory, and Autoimmune Diseases Via Haptenation.
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过敏性、炎症性或自身免疫性疾病的特征是对无害蛋白质如花粉、尘螨和环境中的食物或自身蛋白质的过度免疫反应。在过去50年中，病例数量有所增加。这被认为与减少接触病原微生物有关，以及通过加工食品、配方奶、防腐剂和抗生素接触膳食化学品和药物的革命性增加有关，可能导致对蛋白质的免疫耐受性的破坏。这些化学物质和药物可以作为半抗原发挥作用，半抗原是一种小分子，只有与蛋白质结合时才能引发免疫反应。事实上，越来越多的证据揭示了半抗原参与各种自身免疫样疾病的发展，例如过敏性、炎性或自身免疫性疾病，包括过敏性接触性皮炎、特应性、哮喘、食物过敏、炎性肠病、溶血性贫血、肝损伤、白血病，甚至抗肿瘤免疫。这篇综述强调了最近的进展，这些自身免疫样疾病的化学和药物诱导的发展，通过半抗原结合可能的分子机制和体外测试的替代品，以评估是否提前物质可能导致这些疾病的发展。半抗原是仅在与蛋白质结合时引发免疫应答的小分子。半抗原最初与自身蛋白结合并通过复杂的机制经由炎性细胞因子和损伤相关分子模式以及随后的共刺激信号如树突状细胞上的分化簇86（CD86）的上调来激活先天免疫应答。T细胞上的CD86和CD28之间的后续相互作用对于正确激活初始T细胞和诱导白细胞介素2产生至关重要，从而导致通过效应和记忆T细胞建立适应性免疫。越来越多的证据显示半抗原参与各种自身免疫样疾病的发展，例如过敏性、炎性和自身免疫性疾病，包括过敏性接触性皮炎、特应性、哮喘、食物过敏、炎性肠病、溶血性贫血、肝损伤、白血病，甚至抗肿瘤免疫。因此，非常需要开发体外测试替代品，以提前评估物质是否可能导致这些疾病的发展。本文综述并讨论了化学和药物诱导的过敏性，炎症性和自身免疫性疾病通过半抗原化和可能的分子基础机制，以及在体外测试的替代品，以提前评估是否有物质可能导致这些疾病的发展的最新进展。
Allergic, inflammatory, or autoimmune diseases are characterized by exaggerated immune responses to harmless proteins such as pollen, dust mites, and foods in the environment or self-proteins. The number of cases has increased over the last 50 years. This is considered to be related to reduced exposure to pathogenic microorganisms, as well as a revolutionary rise in exposure to dietary chemicals and drugs via processed food, formula milk, preservatives, and antibiotics, presumably resulting in the breakdown of immune tolerance to proteins. Such chemicals and drugs may work as haptens, which are small molecules that only elicit an immune response when bound to proteins. Indeed, accumulating evidence revealed the involvement of haptens in the development of various autoimmune-like diseases, such as allergic, inflammatory, or autoimmune diseases including allergic contact dermatitis, atopy, asthma, food allergy, inflammatory bowel diseases, hemolytic anemia, liver injury, leukoderma, and even antitumor immunity. This review highlights recent advances in the chemical- and drug-induced development of these autoimmune-like diseases via haptenation together with possible molecular mechanisms and in vitro testing alternatives to evaluate in advance whether a substance might lead to the development of these diseases. Haptens are small molecules that only elicit an immune response when bound to proteins. Haptens initially bind to self-proteins and activate innate immune responses by complex mechanisms via inflammatory cytokines and damage-associated molecular patterns and the subsequent upregulation of costimulatory signals such as cluster of differentiation 86 (CD86) on dendritic cells. Subsequent interactions between CD86 and CD28 on T cells are critically important for properly activating naive T cells and inducing interleukin 2 production, leading to the establishment of adaptive immunity via effector and memory T cells. Accumulating evidence revealed the involvement of haptens in the development of various autoimmune-like diseases such as allergic, inflammatory, and autoimmune diseases including allergic contact dermatitis, atopy, asthma, food allergy, inflammatory bowel diseases, hemolytic anemia, liver injury, leukoderma, and even antitumor immunity. Therefore, the development of in vitro testing alternatives to evaluate in advance whether a substance might lead to the development of these diseases is highly desirable. This review summarizes and discusses recent advances in chemical- and drug-induced allergic, inflammatory, and autoimmune diseases via haptenation and the possible molecular underlying mechanisms, as well as in vitro testing alternatives to evaluate in advance whether a substance might cause the development of these diseases.
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