螺旋体衍生物 Tuftsin-phopshorylcholine，用于治疗自身免疫。

IF 9.2 1区医学 Q1 IMMUNOLOGY

Autoimmunity reviews Pub Date : 2024-10-01 DOI:10.1016/j.autrev.2024.103601

Miri Blank , Yehuda Shoenfeld

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引用次数: 0

摘要

自身免疫性疾病（AIDs）影响着 5-10% 的人口。有大约 100 多种不同的自身免疫性疾病。自身免疫性疾病是导致 65 岁以下女性死亡的十大原因之一；是导致慢性疾病的第二大原因；也是美国女性发病率最高的原因。据美国国立卫生研究院（NIH）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，癌症的直接医疗费用为 570 亿美元，心脏和中风的直接医疗费用为 2000 亿美元。目前治疗自身免疫性疾病的方法包括：类固醇、化疗、免疫抑制剂、生物药物、特定疾病药物（如治疗重症肌无力的乙酰胆碱乙酰胆碱酯酶）。治疗自身免疫性疾病的方法会抑制患者的免疫网络，导致患者更容易受到感染。因此，有必要开发副作用最小的免疫调节小分子药物来治疗自身免疫性疾病。蠕虫会分泌调节人体防御途径的化合物，以便在宿主环境中产生耐受性并存活下来。我们利用蠕虫分泌分子的衍生物模仿了蠕虫的免疫调节活性。我们构建了一种双功能小分子--头孢菌素（T）-磷酰胆碱（PC），被称为 TPC。这种嵌合分子在 4 种自身免疫性疾病小鼠模型中显示出免疫调节活性，通过对宿主免疫系统进行免疫调节，减轻了临床评分和炎症反应。在人外周血单核细胞（PBMCs）和巨细胞动脉炎患者动脉活检组织中的体内试验也证明了这一点。本文揭示了 TPC 免疫调节活性的作用模式。我们的数据表明，这种小分子有望成为治疗自身免疫性疾病患者的一种新型疗法。

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Helminth derivative tuftsin-phopshorylcholine to treat autoimmunity

Autoimmune diseases (AIDs) affect 5 to 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.

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来源期刊

Autoimmunity reviews 医学-免疫学

CiteScore

24.70

自引率

4.40%

发文量

164

审稿时长

21 days

期刊介绍： Autoimmunity Reviews is a publication that features up-to-date, structured reviews on various topics in the field of autoimmunity. These reviews are written by renowned experts and include demonstrative illustrations and tables. Each article will have a clear "take-home" message for readers. The selection of articles is primarily done by the Editors-in-Chief, based on recommendations from the international Editorial Board. The topics covered in the articles span all areas of autoimmunology, aiming to bridge the gap between basic and clinical sciences. In terms of content, the contributions in basic sciences delve into the pathophysiology and mechanisms of autoimmune disorders, as well as genomics and proteomics. On the other hand, clinical contributions focus on diseases related to autoimmunity, novel therapies, and clinical associations. Autoimmunity Reviews is internationally recognized, and its articles are indexed and abstracted in prestigious databases such as PubMed/Medline, Science Citation Index Expanded, Biosciences Information Services, and Chemical Abstracts.