瑞典卡罗林斯卡大学Anna Färnert研究组取得一项新突破。他们的论文发现了临床疟疾的系统分析揭示了与疾病严重程度相关的蛋白质组紊乱和先天适应性串扰。相关论文发表在2025年7月14日出版的《免疫学》杂志上。

研究组分析了成年旅行者急性恶性疟原虫疟疾期间和之后的1463种血浆蛋白，并通过整合来自一小部分供体的单细胞RNA测序（RNA-seq）数据，将其与外周免疫细胞的反应联系起来。研究团队在250多种不同来源的蛋白质中发现了广泛的扰动，包括许多以前未在疟疾患者中分析过的蛋白质，如激素、循环受体、受影响组织的细胞内或膜结合蛋白。蛋白质谱根据疾病严重程度对参与者进行分类，从而能够识别在严重疟疾中富集的压缩11蛋白特征。从概念上讲，这项研究通过将系统蛋白质组学变化与免疫细胞通讯和器官特异性反应联系起来，促进了他们对疟疾的理解。这种抵抗，包括一个互动平台来探索数据，为假设生成，生物标志物发现和治疗靶点识别开辟了新的途径。

据了解，疟疾表现出不同程度的严重程度。了解其发病机制和宿主反应是提高临床管理和预防水平的关键。

附：英文原文

Title: Systems analysis of clinical malaria reveals proteomic perturbation and innate-adaptive crosstalk linked to disease severity

Author: Maximilian Julius Lautenbach, Katja Wyss, Victor Yman, Fariba Foroogh, Donya Satarvandi, Zaynab Mousavian, Klara Sondén, Jun Wang, María Bueno álvez, Sofia Bergstrm, Peter Nilsson, Fredrik Edfors, Petter Brodin, Mathias Uhlén, Christopher Sundling, Anna Frnert

Issue&Volume: 2025-07-14

Abstract: Malaria presents with varying degrees of severity. To improve clinical management and prevention, it is crucial to understand the pathogenesis and host response. We analyzed 1,463 plasma proteins during and after acute Plasmodium falciparum malaria in adult travelers and linked responses to peripheral immune cells by integrating with single-cell RNA sequencing (RNA-seq) data from a subset of donors. We identified extensive perturbations in over 250 proteins with diverse origins, including many not previously analyzed in malaria patients, such as hormones, circulating receptors, and intracellular or membrane-bound proteins from affected tissues. The protein profiles clustered participants according to disease severity, enabling the identification of a compressed 11-protein signature enriched in severe malaria. Conceptually, this study advances our understanding of malaria by linking systemic proteomic changes to immune cell communication and organ-specific responses. This resource, which includes an interactive platform to explore data, opens new avenues for hypothesis generation, biomarker discovery, and therapeutic target identification.

DOI: 10.1016/j.immuni.2025.06.014

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00283-3