Audia Sylvain, Bonnotte Bernard
Service de Médecine Interne et Immunologie Clinique, Centre de Référence Constitutif des Cytopénies Auto-Immunes de l'adulte, Centre Hospitalo-Universitaire Dijon Bourgogne, 21000 Dijon, France.
Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, LabEx LipSTIC, INSERM, EFS BFC, UMR1098, Université de Bourgogne Franche-Comté, 21000 Dijon, France.
J Clin Med. 2021 Mar 2;10(5):1004. doi: 10.3390/jcm10051004.
Immune thrombocytopenia (ITP) is a rare autoimmune disorder caused by peripheral platelet destruction and inappropriate bone marrow production. The management of ITP is based on the utilization of steroids, intravenous immunoglobulins, rituximab, thrombopoietin receptor agonists (TPO-RAs), immunosuppressants and splenectomy. Recent advances in the understanding of its pathogenesis have opened new fields of therapeutic interventions. The phagocytosis of platelets by splenic macrophages could be inhibited by spleen tyrosine kinase (Syk) or Bruton tyrosine kinase (BTK) inhibitors. The clearance of antiplatelet antibodies could be accelerated by blocking the neonatal Fc receptor (FcRn), while new strategies targeting B cells and/or plasma cells could improve the reduction of pathogenic autoantibodies. The inhibition of the classical complement pathway that participates in platelet destruction also represents a new target. Platelet desialylation has emerged as a new mechanism of platelet destruction in ITP, and the inhibition of neuraminidase could dampen this phenomenon. T cells that support the autoimmune B cell response also represent an interesting target. Beyond the inhibition of the autoimmune response, new TPO-RAs that stimulate platelet production have been developed. The upcoming challenges will be the determination of predictive factors of response to treatments at a patient scale to optimize their management.
免疫性血小板减少症（ITP）是一种罕见的自身免疫性疾病，由外周血小板破坏和骨髓生成异常引起。ITP的治疗基于使用类固醇、静脉注射免疫球蛋白、利妥昔单抗、血小板生成素受体激动剂（TPO-RAs）、免疫抑制剂和脾切除术。对其发病机制认识的最新进展开辟了治疗干预的新领域。脾酪氨酸激酶（Syk）或布鲁顿酪氨酸激酶（BTK）抑制剂可抑制脾巨噬细胞对血小板的吞噬作用。通过阻断新生儿Fc受体（FcRn）可加速抗血小板抗体的清除，而针对B细胞和/或浆细胞的新策略可改善致病性自身抗体的减少。参与血小板破坏的经典补体途径的抑制也代表了一个新靶点。血小板去唾液酸化已成为ITP中血小板破坏的一种新机制，抑制神经氨酸酶可减轻这种现象。支持自身免疫性B细胞反应的T细胞也是一个有趣的靶点。除了抑制自身免疫反应外，还开发了刺激血小板生成的新型TPO-RAs。未来的挑战将是确定患者个体对治疗反应的预测因素，以优化治疗管理。
