Identification of Three Distinct Subgroups in Antiphospholipid Syndrome: Implication for Sex Differences and Prognostic Outcomes from a Multicenter Study

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.

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Journal
Advanced Science
Published
2025-02-18
DOI
https://doi.org/10.1002/advs.202415291
Primary Topic
Systemic Lupus Erythematosus Research
Type
article
Field-Weighted Citation Impact
0.00

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article

Identification of Three Distinct Subgroups in Antiphospholipid Syndrome: Implication for Sex Differences and Prognostic Outcomes from a Multicenter Study

Jennifer Cheng, Zhongqiang Yao, Hongjiang Liu, Qing‐Yi Lu et al.
Advanced Science
Systemic Lupus Erythematosus Research
article

Identification of Three Distinct Subgroups in Antiphospholipid Syndrome: Implication for Sex Differences and Prognostic Outcomes from a Multicenter Study

Jennifer Cheng, Zhongqiang Yao, Hongjiang Liu, Qing‐Yi Lu, Yundi Tang, Chao Hou, Yilu Qin, Jianping Guo, Xinxin Li, Chen Chen, Ao Zhang, Chun Li, Xiangjun Liu, Yufei Li, Tianhao Li, Juan Meng, Fangmin Xu, Sai Dong, Ning Xu
article en

Abstract

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.

Advanced ScienceVol. 12(15)
Beijing University of Posts and Telecommunications (CN), Capital Medical University (CN), Peking University (CN), Sichuan University (CN), Beijing Chao-Yang Hospital, Capital Medical University (CN), West China Hospital of Sichuan University (CN), Peking University People's Hospital (CN), Peking University Third Hospital (CN), Xinxiang Central Hospital (CN), Henan Medical University (CN)
National Natural Science Foundation of China, Peking University, Peking University People's Hospital, Medical School, University of Michigan, Peking University Health Science Center
Good health and well-being
Openalex Percentile: Top 95%
Systemic Lupus Erythematosus Research
DOIOpen Access PDFOpenAlex
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