自身免疫性疾病 (AID) 影响 5-10% 的人口。有超过 100 种不同的自身免疫性疾病。艾滋病是 65 岁以下女性十大死因之一；慢性病的第二大原因；美国女性发病的首要原因。美国国立卫生研究院估计，自身免疫性疾病每年的直接医疗费用约为 1000 亿美元，相比之下，癌症投资为 570 亿美元，心脏病和中风费用为 2000 亿美元。目前自身免疫性疾病的治疗方法包括：类固醇、化疗、免疫抑制剂、生物药物、疾病特异性药物（如治疗重症肌无力的乙酰胆碱酯酶）。自身免疫性疾病的治疗会抑制患者的免疫网络，导致患者更容易受到感染。因此，需要开发副作用最小的免疫调节小分子来治疗自身免疫性疾病。蠕虫产生了调节人类防御途径的分泌化合物，以发展耐受性并在宿主环境中生存。我们通过使用蠕虫分泌分子的衍生物来模拟蠕虫的免疫调节活性。构建了一种双功能小分子促吞噬素（T）-磷酸胆碱（PC），简称TPC。这种嵌合分子在 4 个自身免疫性疾病小鼠模型中显示出其免疫调节活性，通过免疫调节宿主免疫系统来减轻临床评分和炎症反应。人外周血单核细胞 (PBMC) 的离体和活检源自巨细胞动脉炎患者的动脉。本文破译了 TPC 免疫调节活性的作用模式。我们的数据表明这种小分子有可能成为自身免疫性疾病患者的新型疗法。版权所有 © 2024。由 Elsevier B.V. 出版。

Autoimmune diseases (AIDs) affect 5-10% of the population . There are more than ~100 different autoimmune diseases. The AIDs are one of the top 10 causes of death in women under 65; 2nd highest cause of chronic illness; top cause of morbidity in women in the US. The NIH estimates annual direct healthcare costs for autoimmune diseases about $100 billion, in comparison, with cancers investment of $57 billion, heart and stroke cost of $200 billion. The current treatments for autoimmune diseases encompasses: steroids, chemotherapy, immunosuppressants, biological drugs, disease specific drugs (like acethylcholine-estherase for myasthenia gravis). The treatments for autooimmune diseases supress the patient immune network, which leads the patients to be more susceptible to infections. Hence, there is a need to develop immunomodulatory small molecules with minimal side effects to treat autoimmune diseases. The helminths developed secreting compounds which modulate the human defense pathways in order to develop tolerance and survive in the host environment. We have imitated the immunomodulatory activity of the helminth by using a derivative of the helminth secretory molecule. A bi-functional small molecule -tuftsin (T)-phosphorylcholine (PC), coined as TPC, was constructed . This chimeric molecule showed its immunomodulatory activity in 4 murine models of autoimmune diseases, attenuating the clinical score and the inflammatory response by immunomodutating the host immune system. Ex-vivo in human peripheral blood mononuclear cells (PBMCs) and biopsies originated from arteries of patients with giant cell arteritis. This paper decipher the mode of action of TPC immunomodulatory activity. Our data propose the potential for this small molecule to be a novel therapy for patients with autoimmune diseases.Copyright © 2024. Published by Elsevier B.V.