OP0038 SPLICEOSOME ALTERATIONS IN LEUCOCYTES FROM APS, SLE AND SLE+APS PATIENTS ARE CLOSELY RELATED TO THEIR MAIN CLINICAL FEATURES

Background: To date, although multiple molecular approaches have illustrated the various aspects of Primary Antiphospholipid Syndrome (APS), systemic lupus erythematosus (SLE) and antiphospholipid syndrome plus (APS SLE), no study has so far fully characterized potential role posttranscriptional regulatory mechanisms such as alternative splicing. Objectives: identify shared differential changes in splicing machinery immune cells from APS, SLE APS patients, their involvement activity clinical profile these autoimmune disorders. Methods: Monocytes, lymphocytes neutrophils 80 patients (22 35 23 SLE) 50 healthy donors (HD) were purified by immunomagnetic selection. Then, selected elements evaluated using a microfluidic qPCR array (Fluidigm). In parallel, extensive clinical/serological evaluation was performed, comprising disease activity, thrombosis renal involvement, along with autoantibodies, acute phase reactants, complement inflammatory molecules. Molecular clustering analyses correlation/association studies developed. Results: Patients primary displayed significant specific alterations components comparison HD, that further for each leukocyte subset. Besides, associated distinctive features. Hence, analysis allowed to two sets representing different groups respect expression levels components. Principal component confirmed clear separation between patients. Clinically, cluster 1 higher thrombotic episodes recurrences than 2 adjusted global score (aGAPSS). Accordingly, showed mediators 2. Similarly, SLE, showing Clinical laboratory profiles had suffered more recurrences, most them displaying an aGAPSS over 12 points expressing 1. The incidence nephropathy similarly represented both clusters. Lastly, identified One positive anti-dsDNA antibodies, suffering nephropathy, high proportion also presenting atheroma plaques mediators. Correlation demonstrated several deranged (i.e. SF3B1tv1, PTBP1, PRP8 RBM17) linked three diseases, albeit way on disorder. vitro treatment HD aPL-IgG or anti-dsDNA-IgG changed spliceosome found altered vivo diseases. Finally, induced over/downregulated leukocytes modulated cytokines, procoagulant/adhesion activities monocytes regulated NETosis neutrophils. Conclusion: 1) machinery, profoundly is closely related profiles. 2) allows segregation explaining CV risk highly Acknowledgements: Funded ISCIII, PI18/00837 RIER RD16/0012/0015 co-funded FEDER Disclosure Interests: None declared