Deciphering Platelet Transcriptomic Profiles in Antiphospholipid Syndrome: Insights into Their Role as Immunological...

Area of Science:

• Immunology
• Hematology
• Systems Biology

Background:

• Antiphospholipid syndrome (APS) is an autoimmune disorder causing thrombosis and pregnancy issues, driven by antiphospholipid antibodies (aPLs).
• Platelets play a key role in APS, but their transcriptomic profile in the disease is not well understood.
• Understanding platelet gene expression is crucial for elucidating APS pathophysiology.

Purpose of the Study:

• To characterize the platelet transcriptomic landscape in APS patients.
• To identify key immune-thrombotic pathways involved in APS pathogenesis.
• To explore potential platelet-based diagnostic markers for APS.

Main Methods:

• RNA sequencing was performed on platelets from 43 APS patients, 20 asymptomatic aPL carriers, and 20 healthy controls.
• Bioinformatic analyses were used to identify differentially expressed genes and pathways.
• A 15-gene classifier was developed and validated for discriminating APS from controls.

Main Results:

• Platelets from APS patients displayed significant proinflammatory transcriptional reprogramming, indicating active thrombo-inflammatory roles.
• Activated innate immune pathways (TLRs, NLRs) and neutrophil pathways were identified in APS platelets.
• A 15-gene classifier accurately distinguished APS patients from controls (AUC 0.901-0.948) and revealed differences between APS and asymptomatic aPL carriers.

Conclusions:

• Platelets in APS exhibit a distinct proinflammatory phenotype, functioning as critical immunothrombotic interfaces.
• These findings support the role of platelets in APS pathogenesis and suggest potential for platelet-derived diagnostic and stratification strategies.
• Distinct molecular signatures were associated with anti-β2-glycoprotein I antibodies and different thrombosis types (arterial vs. venous).