Chen Chen, Zhang Ao, Cheng Jianhui, Yao Zhongqiang, Meng Juan, Qin Yilu, Lu Qingyi, Li Yufei, Liu Xiangjun, Li Tianhao, Hou Chao, Tang Yundi, Liu Hongjiang, Xu Ning, Dong Sai, Li Xinxin, Xu Fangmin, Guo Jianping, Li Chun
Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, 100044, China.
School of Information and Communication Engineering, Beijing University of Posts and Telecommunications, Beijing, 100876, China.
Adv Sci (Weinh). 2025 Apr;12(15):e2415291. doi: 10.1002/advs.202415291. Epub 2025 Feb 18.
Antiphospholipid syndrome (APS) is a heterogeneous autoimmune disease with persistent antiphospholipid antibodies. This study aimed to identify unrecognized APS subgroups from multicenter cohorts (n = 760, training: n = 415; validation: n = 345). Patients are stratified through unsupervised K-means clustering analysis. Prognostic outcomes are evaluated using Kaplan-Meier survival analyses. Proteomic analysis is conducted on primary APS patients (n = 36) and healthy controls (n = 12). Key molecule insulin-like growth factor 1 is validated using ELISA. Three clusters are identified. Cluster 1 (n = 320, 42.1%) is completely consisted of females (100%), with predominant occurrence of pregnancy morbidity (88.8%) but low incidences of thrombocytopenia (18.4%) and thrombosis (15.0%), and a favorable prognosis. Cluster 2 (n = 309, 40.7%) is predominantly female (99.4%) and characterized by high thrombosis (85.8%) and thrombocytopenia (46.6%), low pregnancy morbidity (13.6%), and poor prognosis. Cluster 3 (n = 131, 17.2%) is predominantly male (99.2%), exhibiting highest thrombosis (96.2%) and moderate thrombocytopenia (32.8%), with worst prognosis. Immunological and proteomic analyses clearly differentiated three clusters. This study reveals a distinct difference between obstetric and thrombotic APS, and a sex-based distinction within thrombotic APS. Three APS subgroups display unique clinical and molecular characteristics, and marked difference in prognostic outcomes.
抗磷脂综合征（APS）是一种伴有持续性抗磷脂抗体的异质性自身免疫性疾病。本研究旨在从多中心队列（n = 760，训练组：n = 415；验证组：n = 345）中识别未被认识的APS亚组。通过无监督K均值聚类分析对患者进行分层。使用Kaplan-Meier生存分析评估预后结果。对原发性APS患者（n = 36）和健康对照者（n = 12）进行蛋白质组学分析。使用酶联免疫吸附测定法（ELISA）验证关键分子胰岛素样生长因子1。识别出三个聚类。聚类1（n = 320，42.1%）完全由女性组成（100%），主要发生妊娠并发症（88.8%），但血小板减少症（18.4%）和血栓形成（15.0%）的发生率较低，预后良好。聚类2（n = 309，40.7%）以女性为主（99.4%），其特征为高血栓形成（85.8%）和血小板减少症（46.6%）、低妊娠并发症（13.6%）以及预后不良。聚类3（n = 131，17.2%）以男性为主（99.2%），表现出最高的血栓形成率（96.2%）和中度血小板减少症（32.8%），预后最差。免疫和蛋白质组学分析清楚地区分了三个聚类。本研究揭示了产科APS和血栓形成性APS之间的明显差异，以及血栓形成性APS内基于性别的差异。三个APS亚组表现出独特的临床和分子特征，以及预后结果的显著差异。
