Dysregulation of immune cells and platelet-monocyte aggregates in chronic thromboembolic pulmonary hypertension
Abstract Background Inflammation and immunological dysregulation are involved in the uncommon pulmonary thromboembolism (PTE) consequence known as chronic thromboembolic pulmonary hypertension (CTEPH). Although tissue samples are provided by pulmonary endarterectomy (PEA), accessibility is restricte...
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2025-07-01
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| Online Access: | https://doi.org/10.1186/s12931-025-03284-9 |
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| author | Lu Sun Haobo Li Xincheng Li Yuhan Li Min Liu Han Tian Jixiang Liu Ran Miao Yu Zhang Qiang Huang Zhu Zhang Ximei Niu Shuai Zhang Wanmu Xie Shiqing Xu Peiran Yang Zhenguo Zhai |
| author_facet | Lu Sun Haobo Li Xincheng Li Yuhan Li Min Liu Han Tian Jixiang Liu Ran Miao Yu Zhang Qiang Huang Zhu Zhang Ximei Niu Shuai Zhang Wanmu Xie Shiqing Xu Peiran Yang Zhenguo Zhai |
| author_sort | Lu Sun |
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| description | Abstract Background Inflammation and immunological dysregulation are involved in the uncommon pulmonary thromboembolism (PTE) consequence known as chronic thromboembolic pulmonary hypertension (CTEPH). Although tissue samples are provided by pulmonary endarterectomy (PEA), accessibility is restricted by its technical complexity. Immune cells found in peripheral blood may provide information on how a disease develops. Methods We developed a 7-color flow cytometry method using 200 µl of peripheral blood to analyze immune cell subpopulations and platelet immune cell aggregates in CTEPH. PEA tissues were used for immunofluorescence validation. We employed correlation analysis and linear regression to examine the relationships between immune cell dysregulation and the severity of CTEPH. Results There were 36 age- and sex-matched healthy controls, 10 patients with other subtypes of pulmonary hypertension (PH) except CTEPH, 20 PTE patients, and 62 CTEPH patients. CTEPH patients had markedly dysregulated immune cell subpopulations. There was an increase in T lymphocytes from 60.59 ± 9.94% to 69.05 ± 4.90% (p < 0.0001) in CTEPH patients. Classical monocytes decreased (87.94 ± 9.93% vs. 82.02 ± 9.92%, p < 0.0001), while non-classical monocytes increased (3.69 ± 5.42% vs. 8.44 ± 5.91%, p = 0.02) in CTEPH patients. The same trend was also observed in PH group. Dysregulated immune cells were primarily localized in thrombus and neointima regions. Platelet-monocyte aggregates (PMAs) and their subpopulations were positively correlated with hemodynamic and ultrasound indicators. PTE patients had greater levels of PMAs than CTEPH patients (p = 0.0007), and these levels decreased during treatment (p = 0.0168). Conclusion Immune cell subpopulations in CTEPH can be efficiently analyzed using the low blood volume flow cytometry approach. Peripheral blood immune cell dysregulation points to an active immune response in CTEPH. Insights into the pathophysiology of CTEPH may be gained by using PMA as a biomarker for assessing the severity and treatment outcomes of CTEPH. However, more research is needed to determine PMA's role in CTEPH for disease diagnosis assessment and pathogenesis. |
| format | Article |
| id | doaj-art-e01558a5211744c6adf9b5167bb0462b |
| institution | Kabale University |
| issn | 1465-993X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
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| series | Respiratory Research |
| spelling | doaj-art-e01558a5211744c6adf9b5167bb0462b2025-08-20T03:43:15ZengBMCRespiratory Research1465-993X2025-07-0126111710.1186/s12931-025-03284-9Dysregulation of immune cells and platelet-monocyte aggregates in chronic thromboembolic pulmonary hypertensionLu Sun0Haobo Li1Xincheng Li2Yuhan Li3Min Liu4Han Tian5Jixiang Liu6Ran Miao7Yu Zhang8Qiang Huang9Zhu Zhang10Ximei Niu11Shuai Zhang12Wanmu Xie13Shiqing Xu14Peiran Yang15Zhenguo Zhai16China-Japan Friendship Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeChina-Japan Friendship Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeNational Center for Respiratory MedicineState Key Laboratory of Respiratory Health and Multimorbidity. National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship HospitalChina-Japan Friendship Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Pulmonary and Critical Care Medicine, Affiliated Hospital of Jianghan UniversityNational Center for Respiratory MedicineState Key Laboratory of Respiratory Health and Multimorbidity. National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship HospitalNational Center for Respiratory MedicineState Key Laboratory of Respiratory Health and Multimorbidity. National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship HospitalNational Center for Respiratory MedicineState Key Laboratory of Respiratory Health and Multimorbidity. National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship HospitalNational Center for Respiratory MedicineState Key Laboratory of Respiratory Health and Multimorbidity. National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship HospitalNational Center for Respiratory MedicineState Key Laboratory of Respiratory Health and Multimorbidity. National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship HospitalNational Center for Respiratory MedicineState Key Laboratory of Respiratory Health and Multimorbidity. National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship HospitalNational Center for Respiratory MedicineState Key Laboratory of Respiratory Health and Multimorbidity. National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship HospitalNational Center for Respiratory MedicineState Key Laboratory of Respiratory Health and Multimorbidity. National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship HospitalNational Center for Respiratory MedicineState Key Laboratory of Respiratory Health and Multimorbidity. National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship HospitalNational Center for Respiratory MedicineState Key Laboratory of Respiratory Health and Multimorbidity. National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship HospitalState Key Laboratory of Respiratory Health and Multimorbidity, Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College; National Center for Respiratory Medicine; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; National Clinical Research Center for Respiratory DiseasesNational Center for Respiratory MedicineState Key Laboratory of Respiratory Health and Multimorbidity. National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship HospitalAbstract Background Inflammation and immunological dysregulation are involved in the uncommon pulmonary thromboembolism (PTE) consequence known as chronic thromboembolic pulmonary hypertension (CTEPH). Although tissue samples are provided by pulmonary endarterectomy (PEA), accessibility is restricted by its technical complexity. Immune cells found in peripheral blood may provide information on how a disease develops. Methods We developed a 7-color flow cytometry method using 200 µl of peripheral blood to analyze immune cell subpopulations and platelet immune cell aggregates in CTEPH. PEA tissues were used for immunofluorescence validation. We employed correlation analysis and linear regression to examine the relationships between immune cell dysregulation and the severity of CTEPH. Results There were 36 age- and sex-matched healthy controls, 10 patients with other subtypes of pulmonary hypertension (PH) except CTEPH, 20 PTE patients, and 62 CTEPH patients. CTEPH patients had markedly dysregulated immune cell subpopulations. There was an increase in T lymphocytes from 60.59 ± 9.94% to 69.05 ± 4.90% (p < 0.0001) in CTEPH patients. Classical monocytes decreased (87.94 ± 9.93% vs. 82.02 ± 9.92%, p < 0.0001), while non-classical monocytes increased (3.69 ± 5.42% vs. 8.44 ± 5.91%, p = 0.02) in CTEPH patients. The same trend was also observed in PH group. Dysregulated immune cells were primarily localized in thrombus and neointima regions. Platelet-monocyte aggregates (PMAs) and their subpopulations were positively correlated with hemodynamic and ultrasound indicators. PTE patients had greater levels of PMAs than CTEPH patients (p = 0.0007), and these levels decreased during treatment (p = 0.0168). Conclusion Immune cell subpopulations in CTEPH can be efficiently analyzed using the low blood volume flow cytometry approach. Peripheral blood immune cell dysregulation points to an active immune response in CTEPH. Insights into the pathophysiology of CTEPH may be gained by using PMA as a biomarker for assessing the severity and treatment outcomes of CTEPH. However, more research is needed to determine PMA's role in CTEPH for disease diagnosis assessment and pathogenesis.https://doi.org/10.1186/s12931-025-03284-9Chronic thromboembolic pulmonary hypertensionFlow cytometryImmune cellPlatelet-monocyte aggregateDisease SeverityPathogenesis |
| spellingShingle | Lu Sun Haobo Li Xincheng Li Yuhan Li Min Liu Han Tian Jixiang Liu Ran Miao Yu Zhang Qiang Huang Zhu Zhang Ximei Niu Shuai Zhang Wanmu Xie Shiqing Xu Peiran Yang Zhenguo Zhai Dysregulation of immune cells and platelet-monocyte aggregates in chronic thromboembolic pulmonary hypertension Respiratory Research Chronic thromboembolic pulmonary hypertension Flow cytometry Immune cell Platelet-monocyte aggregate Disease Severity Pathogenesis |
| title | Dysregulation of immune cells and platelet-monocyte aggregates in chronic thromboembolic pulmonary hypertension |
| title_full | Dysregulation of immune cells and platelet-monocyte aggregates in chronic thromboembolic pulmonary hypertension |
| title_fullStr | Dysregulation of immune cells and platelet-monocyte aggregates in chronic thromboembolic pulmonary hypertension |
| title_full_unstemmed | Dysregulation of immune cells and platelet-monocyte aggregates in chronic thromboembolic pulmonary hypertension |
| title_short | Dysregulation of immune cells and platelet-monocyte aggregates in chronic thromboembolic pulmonary hypertension |
| title_sort | dysregulation of immune cells and platelet monocyte aggregates in chronic thromboembolic pulmonary hypertension |
| topic | Chronic thromboembolic pulmonary hypertension Flow cytometry Immune cell Platelet-monocyte aggregate Disease Severity Pathogenesis |
| url | https://doi.org/10.1186/s12931-025-03284-9 |
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