Clinical value of soluble fms-like tyrosine kinase 1 (sFlt-1) in adult secondary hemophagocytic lymphohistiocytosis

Sep 29, 2026

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Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening syndrome driven by an excessive systemic inflammatory response, often leading to multiple organ dysfunction and limited prognostic immune biomarkers. This study evaluates soluble fms-like tyrosine kinase 1 (sFlt-1), an inflammation-associated marker, by measuring Flt-1 expression in peripheral CD14+ monocytes and plasma sFlt-1 using flow cytometry and ELISA across adult patients enrolled retrospectively.

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J Chin MedAssoc Original article Clinical value of soluble fms-like tyrosine kinase 1 (sFlt-1) in adult secondary hemophagocytic lymphohistiocytosis Wanying Chenga,b, Lingling Wanga,d, Xin Gaoa, Guangli Yina, Jujuan Wanga, Yongqian Shuc, Hongxia Qiua,b,* , Limin Duana,b,* aDepartment of Geriatric Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China; bDepartment of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China; cDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China; dDepartment of Hematology, Wuxi People’s Hospital, Wuxi, China Abstract Background: Secondary hemophagocytic lymphohistiocytosis (sHLH) is a syndrome characterized by an excessive systemic inflammatory response, manifested by multiple organ dysfunction, lacking reliable immune biomarkers for predicting their inflammatory status and prognosis. Soluble fms-like tyrosine kinase 1 (sFlt-1) is associated with various inflammation-related diseases, including sepsis and severe organ failure. Methods: This study retrospectively included 32 adult sHLH patients diagnosed from January 2020 to December 2021. The expression of Flt-1 in peripheral blood CD14+ monocytes was detected by flow cytometry, and the level of plasma sFlt-1 was detected by ELISA. Results: In our study, the results of flow cytometry reveal that the Flt-1 expression on CD14+ monocytes of peripheral blood from sHLH patients was higher than that in normal control. In plasma samples of sHLH patients, sFlt-1 levels were 677.8 (463 .2–929.7) pg/mL, significantly higher than in normal controls 377.18 (350 .4–424.6) pg/mL and sepsis group 378.3 (257 .0–499. 1) pg/mL. Besides, a positive correlation was found between sFlt-1 and IL-6 in sHLH patients. The analysis of univariate Cox regression indicated that sFlt-1 >681 .5 pg/mL demonstrated unfavorable overall survival (p = 0 .022) . Multivariate analysis demonstrated that sFlt-1 >681 .5 pg/mL was an independent factor associated with OS (p = 0 .041) after adjustment for confounders. Restricted cubic spline confirmed a linear and positive association between sFlt-1 and mortality risk. Conclusion: Retrospective analysis showed that sFlt-1 was a promising prognostic factor. Keywords: Fms-like tyrosine kinase 1; Prognosis; Secondary hemophagocytic lymphohistiocytosis 1. INTRODUCTION Adult secondary hemophagocytic lymphohistiocytosis (sHLH) is a rare but potentially fatal disorder characterized by an excessive activation and proliferation of macrophages and T lymphocytes. These activated immune cells produce many proinflammatory cytokines, known as a “cytokine storm.”1 Various clinical signs and symptoms associated with abnormal cytokines are fever, hepatomegaly, splenomegaly, hemorrhagic manifestations, and * Address correspondence. Dr. Hongxia Qiu, Department of Geriatric Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, [China. E-mail address: qhx9805@126.com](China. E-mail address: qhx9805@126.com) (H. Qiu); Dr. Limin Duan, Department of Geriatric Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China. E-mail address: [duanliminde@163.com](duanliminde@163.com) (L. Duan). Author contributions: Dr. Wanying Cheng and Dr. Lingling Wang contributed equally to this work. Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article. Journal of Chinese Medical Association. (2023) 86: 659-664. Received December 28, 2022; accepted March 23, 2023. doi: 10. 1097/JCMA.0000000000000943. Copyright © 2023, the Chinese Medical Association. This is an open access article under the CC BY-NC-ND license ([http://creativecommons.org/licenses/by-

FAQs

What is the clinical focus of measuring sFlt-1 in adult sHLH?

The study focuses on whether sFlt-1 reflects disease inflammatory activity and can serve as a prognostic indicator for adult secondary hemophagocytic lymphohistiocytosis.

How were Flt-1 and sFlt-1 levels measured in the study?

Flt-1 expression on peripheral blood CD14+ monocytes was detected by flow cytometry, and plasma sFlt-1 levels were measured by ELISA.

What did the results show about sFlt-1 levels and outcomes?

Plasma sFlt-1 was significantly higher in adult sHLH than in normal controls and a sepsis group. A threshold of sFlt-1 > 681.5 pg/mL was associated with unfavorable overall survival and remained an independent risk factor after adjustment.

Sep 29, 2026

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