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Abstract：
TAFRO (thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (F/R), renal failure (R), and organomegaly (O)) is a heterogeneous clinical subtype of idiopathic multicentric Castleman disease (iMCD) associated with a significantly poorer prognosis than other subtypes of iMCD. TAFRO symptomatology can also be seen in pathological contexts outside of iMCD, but it is unclear if those cases should be considered representative of a different disease entity or simply a severe presentation of other infectious, malignant, and rheumatological diseases. While interleukin-6 (IL-6) is an established driver of iMCD-TAFRO pathogenesis in a subset of patients, the etiology is unknown. Recent case reports and literature reviews on TAFRO patients suggest that vascular endothelial growth factor (VEGF), and the interplay of VEGF and IL-6 in concert, rather than IL-6 as a single cytokine, may be drivers for iMCD-TAFRO pathophysiology, especially renal injury. In this review, we discuss the possible role of VEGF in the pathophysiology and clinical manifestations of iMCD-TAFRO. In particular, VEGF may be involved in iMCD-TAFRO pathology through its ability to activate RAS/RAF/MEK/ERK and PI3K/AKT/mTOR signaling pathways. Further elucidating a role for the VEGF-IL-6 axis and additional disease drivers may shed light on therapeutic options for the treatment of TAFRO patients who do not respond to, or otherwise relapse following, treatment with IL-6 targeting drugs. This review investigates the potential role of VEGF in the pathophysiology of iMCD-TAFRO and the potential for targeting related signaling pathways in the future.
摘要：
TAFRO（血小板减少症（T），anasarca(A),发烧（F），网织蛋白纤维化（F/R），肾功能衰竭(R),和器官肿大（O））是特发性多中心Castleman病（iMCD）的异质性临床亚型，与iMCD的其他亚型相比，其预后明显较差。TAFRO症状学也可以在iMCD之外的病理环境中看到，但目前还不清楚这些病例是否应该被认为是代表不同的疾病实体，或者仅仅是其他传染病的严重表现，恶性,和风湿病。虽然白细胞介素-6（IL-6）是iMCD-TAFRO发病机制的既定驱动因素，病因不明。最近关于TAFRO患者的病例报道和文献综述提示血管内皮生长因子(VEGF),以及VEGF和IL-6的相互作用，而不是作为单一细胞因子的IL-6，可能是iMCD-TAFRO病理生理学的驱动程序,尤其是肾损伤。在这次审查中,我们讨论了VEGF在iMCD-TAFRO的病理生理和临床表现中的可能作用。特别是,VEGF可能通过其激活RAS/RAF/MEK/ERK和PI3K/AKT/mTOR信号通路的能力参与iMCD-TAFRO病理。进一步阐明VEGF-IL-6轴的作用和其他疾病驱动因素可能会阐明治疗TAFRO患者的治疗选择，或以其他方式复发，用IL-6靶向药物治疗。本文综述了VEGF在iMCD-TAFRO病理生理学中的潜在作用以及未来靶向相关信号通路的潜力。
