C3 as a predictive and prognostic biomarker in adult hemophagocytic lymphohistiocytosis: a large cohort study in China

Abstract: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome. Complement component 3 (C3), a central effector molecule in 3 separate complement pathways, has been linked to inflammatory diseases. Hence, we aimed to investigate the clinical significance of C3 in...

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Main Authors: Xuemei Shu, Xinjie Gao, Yujun Dai, Yuxiang Wang, Yilin Liu, Dawei Wang, Tao Guo
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:Blood Advances
Online Access:http://www.sciencedirect.com/science/article/pii/S2473952925000898
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author Xuemei Shu
Xinjie Gao
Yujun Dai
Yuxiang Wang
Yilin Liu
Dawei Wang
Tao Guo
author_facet Xuemei Shu
Xinjie Gao
Yujun Dai
Yuxiang Wang
Yilin Liu
Dawei Wang
Tao Guo
author_sort Xuemei Shu
collection DOAJ
description Abstract: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome. Complement component 3 (C3), a central effector molecule in 3 separate complement pathways, has been linked to inflammatory diseases. Hence, we aimed to investigate the clinical significance of C3 in adult HLH. In this retrospective cohort study, patients meeting ≥5 of 8 HLH-2004 criteria were classified as the HLH group (n = 627), whereas those meeting 1 to 4 criteria were the partial HLH group (n = 588). C3 was significantly lower in the HLH group than the partial HLH group (P < .0001), and low C3 was an independent factor predicting progression from partial HLH to HLH (odds ratio, 3.94; P < .001). Low C3 was associated with more severe cytopenia, coagulation abnormalities, and liver dysfunction. Additionally, patients with low C3 had poorer overall survival (P = .00099), and low C3 was an independent risk factor for early death in HLH (hazard ratio, 1.64; P = .019). Most patients with HLH had normal C3 before HLH onset, followed by a decline after HLH development (P < .0001). Moreover, survivors showed an increase in C3 (P = .0003), whereas nonsurvivors exhibited a decrease in C3 (P = .90). In conclusion, our study identified C3 as a valuable predictive and prognostic biomarker in adult HLH. Monitoring the dynamic changes in C3 levels may reflect therapeutic response and guide timely clinical interventions.
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spelling doaj-art-69dda5618007403eadadfff2880eac532025-08-20T03:08:50ZengElsevierBlood Advances2473-95292025-04-01981836184610.1182/bloodadvances.2024014715C3 as a predictive and prognostic biomarker in adult hemophagocytic lymphohistiocytosis: a large cohort study in ChinaXuemei Shu0Xinjie Gao1Yujun Dai2Yuxiang Wang3Yilin Liu4Dawei Wang5Tao Guo6Department of Hematology, Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Hematology, Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Second Clinical College, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Hematology, Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Hematology, Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Hematology, Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Correspondence: Dawei Wang, Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No.197 Ruijin Second Road, Shanghai 200025, China;Department of Hematology, Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, Wuhan, China; Tao Guo, Institute of Hematology, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Jiefang Dadao 1277, Wuhan 430022, China;Abstract: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome. Complement component 3 (C3), a central effector molecule in 3 separate complement pathways, has been linked to inflammatory diseases. Hence, we aimed to investigate the clinical significance of C3 in adult HLH. In this retrospective cohort study, patients meeting ≥5 of 8 HLH-2004 criteria were classified as the HLH group (n = 627), whereas those meeting 1 to 4 criteria were the partial HLH group (n = 588). C3 was significantly lower in the HLH group than the partial HLH group (P < .0001), and low C3 was an independent factor predicting progression from partial HLH to HLH (odds ratio, 3.94; P < .001). Low C3 was associated with more severe cytopenia, coagulation abnormalities, and liver dysfunction. Additionally, patients with low C3 had poorer overall survival (P = .00099), and low C3 was an independent risk factor for early death in HLH (hazard ratio, 1.64; P = .019). Most patients with HLH had normal C3 before HLH onset, followed by a decline after HLH development (P < .0001). Moreover, survivors showed an increase in C3 (P = .0003), whereas nonsurvivors exhibited a decrease in C3 (P = .90). In conclusion, our study identified C3 as a valuable predictive and prognostic biomarker in adult HLH. Monitoring the dynamic changes in C3 levels may reflect therapeutic response and guide timely clinical interventions.http://www.sciencedirect.com/science/article/pii/S2473952925000898
spellingShingle Xuemei Shu
Xinjie Gao
Yujun Dai
Yuxiang Wang
Yilin Liu
Dawei Wang
Tao Guo
C3 as a predictive and prognostic biomarker in adult hemophagocytic lymphohistiocytosis: a large cohort study in China
Blood Advances
title C3 as a predictive and prognostic biomarker in adult hemophagocytic lymphohistiocytosis: a large cohort study in China
title_full C3 as a predictive and prognostic biomarker in adult hemophagocytic lymphohistiocytosis: a large cohort study in China
title_fullStr C3 as a predictive and prognostic biomarker in adult hemophagocytic lymphohistiocytosis: a large cohort study in China
title_full_unstemmed C3 as a predictive and prognostic biomarker in adult hemophagocytic lymphohistiocytosis: a large cohort study in China
title_short C3 as a predictive and prognostic biomarker in adult hemophagocytic lymphohistiocytosis: a large cohort study in China
title_sort c3 as a predictive and prognostic biomarker in adult hemophagocytic lymphohistiocytosis a large cohort study in china
url http://www.sciencedirect.com/science/article/pii/S2473952925000898
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