POS1004 COULD PLATELET-DERIVED EXTRACELLULAR VESICLES BE A SOURCE OF CLASSICAL AUTOANTIGENS IN SJÖGREN’S SYNDROME PATIENTS?
Authors: A. C. Duchez, L. Bruyere, E. Delrue, F. Cognasse, S. Paul, M. Killian
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Platelet are small anucleate circulating cell in blood. They are well known for their hemostatic function, less for their immune function (which has previously been identified in autoimmune conditions such as rheumatoid arthritis and systemic lupus) and their high potential to release extracellular vesicles (EVs). EVs are small membrane vesicles, generated from the budding of membrane (large EVs, mainly microvesicles (MV) and apoptotic bodies, size between 100nm to 1000nm) or from the exocytosis of multivesicular bodies (small EVs, mainly exosomes, size between 30 to 1000nm). These EVs are considered as potent biomarkers of different pathologies. We hypothesized that EVs from platelet could express different markers of Sjögren's syndrome (SjS), including classical autoantigens possibly contributing to SjS' pathophysiology, and could be good candidates as biomarkers, especially if detectable in routinely collected serum (whereas most EVs-related studies use plasma). <h3>Objectives:</h3> The main goal of our pilot study was to evaluate platelet-derived MV in the serum of SjS patients and relevant controls, in terms of quantity and phenotypes <h3>Methods:</h3> The "I GET DRY" study (NCT03003572) biobank was used to source serum from SjS patients, divided in an inactive/low activity (ESSDAI&lt;5) and an active (ESSDAI≥5) group, and non-SjS sicca patients (<i>i.e.,</i> patients with sicca syndrome not fulfilling the ACR/EULAR 2016 classification criteria for SjS). Serum from healthy blood donors were used as controls. Each sample was first characterized with Dynamic Light Scatter (DLS; Malvern), to evaluate the size of EVs. Then spectral flow cytometry-based (Cytek Northern Light) characterization of EVs (cell source, protein expression) was performed with antibodies against CD41 (to identify platelet-derived EVs), CD32a/FcγRIIa, Ro60/Trove2, Ro52/Trim21, La/SSB, and Annexin V (to identify EVs via the binding of membrane-exposed phosphatidylserine [PS]). <h3>Results:</h3> DLS experiments identified large EVs (mainly MVs) and small EVs as the main components of serum EVs in the four groups, without significant differences between them. Pilot flow cytometry experiments, did not identify significant group differences either regarding the amount of platelet-derived (CD41+ PS+) MVs, however, the expression of the 3 classical autoantigens (Ro60, Ro52 and La) on these MVs was increased in SjS patients (both active and inactive) compared to corresponding expression in non-SjS sicca patients and heathy donors. <h3>Conclusion:</h3> Platelets and platelet-derived MVs are globally understudied despite their known role in some immune and inflammatory pathologies. Here, our pilot study brings interesting insight about a possible new role of platelet-derived MVs as a source of autoantigens, which could contribute, to the autoimmune response in SjS. These results needs to be confirme in larger studies. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>