Single-cell transcriptomic analysis reveals distinct plasma cell populations in chronic thromboembolic pulmonary hypertension.

IF 5.5 2区医学 Q1 HEMATOLOGY

Journal of Thrombosis and Haemostasis Pub Date : 2025-02-16 DOI:10.1016/j.jtha.2025.02.010

Rui Zhang, Yunlong Zhang, Huiting Li, Jing Zhang, Qiao Feng, Yitong Lei, Sihan Liu, Qinhua Zhao, Jing He, Cijun Luo, Hongling Qiu, Jianfeng Zhang, Sugang Gong, Lan Wang

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引用次数: 0

Abstract

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) presents challenges due to its complex pathobiology. Although numerous studies have reported heterogeneous cell types by single-cell RNA sequencing, the atlas and characteristics of plasma cells remain poorly understood.

Objectives: To identify the altered phenotype and differentiation patterns of plasma cells in CTEPH.

Methods: We performed single-cell RNA sequencing on pulmonary endarterectomy tissue from 5 patients and 6 normal pulmonary arteries. Serum immunoglobulins (Igs) were measured using protein electrophoresis among 273 CTEPH patients, 259 idiopathic pulmonary arterial hypertension (IPAH) patients, and 251 healthy controls.

Results: The percentage of plasma cells was significantly increased from less than 1% in healthy controls to 15% in CTEPH patients. We identified 1 B cell cluster and 5 distinct mature plasma cell clusters, including IGHG1, HSPA1A, AHNAK, IGLC3, and IGKV4. Notably, the AHNAK and IGLC3 subclusters are newly identified. GeneSwitches analysis indicated early activation of IGHG1 and early deactivation of HLA-DPA1. The trajectory of AHNAK cluster was earlier than that of IGLC3 cluster, with an enrichment for pathways responsive to lipopolysaccharide. The IGLC3 cluster revealed lower differentiation potential and was predominantly associated with Ig production. Furthermore, Igα2 levels in CTEPH patients were lower than in controls but higher than in IPAH patients. Significantly, Igγ levels were markedly elevated in CTEPH patients compared with IPAH patients and controls, better distinguishing CTEPH patients from controls and IPAH patients.

Conclusion: Plasma cells of CTEPH had a distinctive landscape and heterogeneity. The newly identified clusters represented excessive Ig production but lacked immune response function. These findings highlight that targeted plasma cells can be used to develop novel CTEPH treatments.

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来源期刊

Journal of Thrombosis and Haemostasis 医学-外周血管病

CiteScore

24.30

自引率

3.80%

发文量

321

审稿时长

1 months

期刊介绍： The Journal of Thrombosis and Haemostasis (JTH) serves as the official journal of the International Society on Thrombosis and Haemostasis. It is dedicated to advancing science related to thrombosis, bleeding disorders, and vascular biology through the dissemination and exchange of information and ideas within the global research community. Types of Publications: The journal publishes a variety of content, including: Original research reports State-of-the-art reviews Brief reports Case reports Invited commentaries on publications in the Journal Forum articles Correspondence Announcements Scope of Contributions: Editors invite contributions from both fundamental and clinical domains. These include: Basic manuscripts on blood coagulation and fibrinolysis Studies on proteins and reactions related to thrombosis and haemostasis Research on blood platelets and their interactions with other biological systems, such as the vessel wall, blood cells, and invading organisms Clinical manuscripts covering various topics including venous thrombosis, arterial disease, hemophilia, bleeding disorders, and platelet diseases Clinical manuscripts may encompass etiology, diagnostics, prognosis, prevention, and treatment strategies.