Molecular blueprints: Unmasking four distinct immune profiles in antiphospholipid syndrome
A new study published in *Arthritis & Rheumatology* has used whole-blood RNA sequencing to define four distinct molecular endotypes in patients positive for antiphospholipid antibodies (aPL). By analyzing the transcriptomes of 174 individuals, researchers identified clusters ranging from a lymphoid-predominant, metabolically active profile to a myeloid-dominant cluster characterized by strong activation of inflammatory pathways like mTOR, NETosis, and Hippo/IL-6 signaling. This latter cluster, associated with higher neutrophil counts and specific clinical features, represents a more aggressive disease phenotype. The research moves beyond clinical classification to reveal the underlying immune cell landscapes and pathway dysregulations that drive the thromboinflammatory disorder.
Why it might matter to you: This work represents a significant step toward precision medicine in autoimmune and thrombotic disorders. For immunologists and clinicians, it provides a framework for stratifying patients based on their dominant immune pathways—such as myeloid inflammation or lymphoid regulation—rather than broad clinical labels. This molecular stratification could directly inform the development of targeted therapies, such as pathway-specific inhibitors, and improve patient selection for clinical trials, moving the field beyond one-size-fits-all treatment approaches.
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