Identification of Three Distinct Subgroups in Antiphospholipid Syndrome: Implication for Sex Differences and...

Area of Science:

• Autoimmune Diseases
• Immunology
• Genetics and Genomics

Background:

• Antiphospholipid syndrome (APS) is a complex autoimmune disorder characterized by persistent antiphospholipid antibodies.
• Existing classifications may not fully capture the heterogeneity of APS, impacting patient outcomes.

Purpose of the Study:

• To identify and characterize novel subgroups within antiphospholipid syndrome (APS) using multicenter patient cohorts.
• To elucidate the distinct clinical manifestations, molecular profiles, and prognostic outcomes of these identified APS subgroups.

Main Methods:

• Unsupervised K-means clustering was employed to stratify 760 patients from multicenter cohorts.
• Kaplan-Meier survival analyses were used to evaluate prognostic outcomes.
• Proteomic analysis and ELISA were conducted to identify key molecular differences, including insulin-like growth factor 1.

Main Results:

• Three distinct APS subgroups were identified: Cluster 1 (obstetric focus, favorable prognosis), Cluster 2 (thrombotic focus, poor prognosis), and Cluster 3 (male-predominant thrombotic, worst prognosis).
• Significant differences in clinical features (pregnancy morbidity, thrombosis, thrombocytopenia) and molecular markers were observed between clusters.
• Proteomic and immunological analyses confirmed the distinct nature of the three subgroups.

Conclusions:

• This research reveals three unique antiphospholipid syndrome (APS) subgroups with distinct clinical and molecular signatures.
• The findings highlight a clear differentiation between obstetric and thrombotic APS, as well as a sex-based distinction within thrombotic APS.
• These identified subgroups offer a refined understanding of APS heterogeneity, paving the way for more targeted therapeutic approaches and improved patient prognostication.