Autoimmune pathogenesis, immunosuppressive therapy and pharmacological mechanism in aplastic anemia.

IF 4.8 2区医学 Q2 IMMUNOLOGY International immunopharmacology Pub Date : 2023-04-01 DOI:10.1016/j.intimp.2023.110036

Pengpeng Pan, Congcong Chen, Jian Hong, Yue Gu

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引用次数: 2

Abstract

Acquired aplastic anemia (AA) is an autoimmune disease of bone marrow failure mediated by abnormally activated T cells, manifested by severe depletion of hematopoietic stem and progenitor cells (HSPCs) and peripheral blood cells. Due to the limitation of donors for hematopoietic stem cell transplantation, immunosuppressive therapy (IST) is currently an effective first-line treatment. However, a significant proportion of AA patients remain ineligible for IST, relapse, and develop other hematologic malignancies, such as acute myeloid leukemia after IST. Therefore, it is important to elucidate the pathogenic mechanisms of AA and to identify treatable molecular targets, which is an attractive way to improve these outcomes. In this review, we summarize the immune-related pathogenesis of AA, pharmacological targets, and clinical effects of the current mainstream immunosuppressive agents. It provides new insight into the combination of immunosuppressive drugs with multiple targets, as well as the discovery of new druggable targets based on current intervention pathways.

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再生障碍性贫血的自身免疫发病机制、免疫抑制治疗及药理机制。

获得性再生障碍性贫血(AA)是一种由异常活化的T细胞介导的骨髓衰竭的自身免疫性疾病，表现为造血干细胞和祖细胞(HSPCs)和外周血细胞的严重耗竭。由于造血干细胞移植供体的限制，免疫抑制疗法(IST)是目前有效的一线治疗方法。然而，相当比例的AA患者仍然不适合IST，复发，并在IST后发展为其他血液系统恶性肿瘤，如急性髓系白血病。因此，阐明AA的致病机制和确定可治疗的分子靶点是改善这些结果的重要途径。本文就AA的免疫相关发病机制、目前主流免疫抑制剂的药理靶点及临床疗效进行综述。它为免疫抑制药物与多靶点的组合提供了新的见解，以及基于当前干预途径发现新的可药物靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.