Farhid Fatemeh, Rezaeeyan Hadi, Habibi Reza, Kamali Yazdi Ehsan, Hamblin Michael R, Naghinezhad Jalal
Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Iranian Blood Transfusion Organization Building, Next to the Milad Tower, Hemmat Exp. Way, P.O.Box:14665-1157, Tehran, Iran.
Asadabad School of Medical Sciences, Asadabad, Iran.
J Transl Autoimmun. 2025 Aug 19;11:100309. doi: 10.1016/j.jtauto.2025.100309. eCollection 2025 Dec.
Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disorder characterized by immune-mediated destruction of platelets and impaired platelet production. Although autoantibodies have historically been central to the understanding of ITP, current evidence demonstrates that its pathogenesis extends well beyond humoral mechanisms to involve complex dysregulation of both innate and adaptive immune responses. Multiple immune pathways-including autoreactive B and T cells, dendritic cell activation, and regulatory T cell deficiency-contribute to disease onset, progression, and chronicity. Moreover, ITP encompasses a broad spectrum of clinical and immunological subtypes, including primary idiopathic forms and secondary ITP associated with autoimmune diseases, infections, and inborn errors of immunity. This review offers a novel perspective on ITP pathogenesis, emphasizing the active immunoregulatory role of platelets as contributors to immune dysregulation. Far from being passive targets, platelets in ITP actively shape immune responses through crosstalk with immune cells, particularly CD4 T helper (Th) and CD8 cytotoxic T cells. This interaction, primarily mediated via the P-selectin-PSGL-1 axis, promotes Th1/Th17 polarization, enhances autoantibody production, and accelerates platelet destruction. In parallel, platelet-derived microparticles (PMPs) act as potent immune effectors by delivering pro-inflammatory cytokines and autoantigens that sustain chronic immune activation. Prolonged platelet activation also gives rise to a distinct subpopulation known as "hairy platelets"-exhausted, granule-depleted cells with altered surface phenotypes and sustained pro-inflammatory potential. Although functionally exhausted in terms of coagulation, these platelets retain immunostimulatory capacity through persistent phosphatidylserine exposure and cytokine release. By reframing platelets as active participants in the pathogenesis of ITP, this review proposes that targeting platelet activation, platelet-T cell interactions, and PMP release may represent innovative therapeutic strategies. Such approaches could offer more precise and personalized treatment options, particularly for patients with chronic or refractory disease, by restoring immune balance and improving long-term outcomes.
免疫性血小板减少症（ITP）是一种异质性自身免疫性疾病，其特征为免疫介导的血小板破坏和血小板生成受损。尽管自身抗体在历史上一直是理解ITP的核心，但目前的证据表明，其发病机制远不止体液机制，还涉及先天性和适应性免疫反应的复杂失调。多种免疫途径——包括自身反应性B细胞和T细胞、树突状细胞活化以及调节性T细胞缺陷——都与疾病的发生、发展和慢性化有关。此外，ITP涵盖了广泛的临床和免疫亚型，包括原发性特发性形式以及与自身免疫性疾病、感染和先天性免疫缺陷相关的继发性ITP。本综述提供了关于ITP发病机制的新观点，强调血小板作为免疫失调促成因素的积极免疫调节作用。在ITP中，血小板绝非被动靶点，而是通过与免疫细胞，特别是CD4辅助性T（Th）细胞和CD8细胞毒性T细胞的相互作用，积极塑造免疫反应。这种相互作用主要通过P-选择素-PSGL-1轴介导，促进Th1/Th17极化，增强自身抗体产生，并加速血小板破坏。同时，血小板衍生微粒（PMPs）通过传递维持慢性免疫激活的促炎细胞因子和自身抗原，充当强大的免疫效应器。血小板的长期活化还会产生一种独特的亚群，称为“毛细胞血小板”——耗尽、颗粒缺失的细胞，其表面表型改变且具有持续的促炎潜力。尽管这些血小板在凝血功能方面已耗尽，但它们通过持续暴露磷脂酰丝氨酸和释放细胞因子仍保留免疫刺激能力。通过将血小板重新定位为ITP发病机制中的积极参与者，本综述提出，靶向血小板活化、血小板-T细胞相互作用和PMP释放可能代表创新的治疗策略。这些方法可以通过恢复免疫平衡和改善长期预后，提供更精确和个性化的治疗选择，特别是对于慢性或难治性疾病患者。
