Characterisation of Platelet Releasate Proteome in Relapsing-Remitting Multiple Sclerosis Reveals Dysregulation of Inflammatory Signalling and Extracellular Vesicle Dynamics.

Purpose: Multiple Sclerosis is an inflammatory neurodegenerative disease characterised by blood-brain barrier dysfunction and leukocyte infiltration into the CNS. Platelets are best known for their contributions to haemostasis, however, upon activation, platelets release an abundance of soluble and vesicular-associated proteins, termed the platelet releasate (PR). This milieu contains numerous inflammatory and vasoactive proteins, that can attract leukocytes and alter endothelial permeability.

Experimental design: We aimed to characterise the PR of Relapsing-Remitting multiple sclerosis (RRMS) patients, previously characterized regarding thrombin generation dynamics compared to healthy controls. We carried out LFQ proteomic profiling of the PR from 15 RRMS and 19 aged-matched healthy controls.

Results: We identified 9 proteins increased and 16 proteins decreased in the PR of RRMS patients. Platelet/endothelial cell-adhesion molecule-1 (PECAM-1) was uniquely found in healthy control PR and circulating levels of PECAM-1 were significantly lower in RRMS patient samples. GO analysis revealed a strong link between altered proteins and extracellular vesicles (EVs). Small EV levels were significantly reduced in RRMS PR compared to healthy PR and showed a negative correlation with PECAM-1 levels in RRMS plasma.

Conclusions and clinical relevance: Our findings suggest that platelet reactivity may be linked to disease activity, even in periods of disease remission.