POS1409 NEW INSIGHTS INTO THE ANTIPHOSPHOLIPID SYNDROME SPECTRUM: FROM ANTIPHOSPHOLIPID ANTIBODIES POSITIVE SUBJECTS PROFILING TO IDENTIFICATION OF SYSTEMIC APS SUBSET THROUGH TYPE I INTERFERON PATHWAY ACTIVATION

Background Type I Interferon (IFN) pathway activation plays a central role in the pathogenesis of several autoimmune conditions. However, limited evidence is available on IFN antiphospholipid antibody (aPL) positive subjects, including aPL carriers and syndrome (APS) patients. In addition, recent evidences have highlighted existence bridging condition between pure primary APS (PAPS) defined systemic lupus erythematosus (SLE) with higher general features, such as cytopenia arthritis, which known [1] needs further clarification. Objectives The aim this study was to evaluate differential expression stimulated genes (ISG) among different subsets subjects. Methods For purpose study, 31 APS, 25 secondary (SAPS), 27 SLE patients without aPL, 29 [2,3] 19 healthy controls (HCs) were recruited. Complete demographic, clinical, laboratory data collected at time inclusion. Systemic previous papers . IFI6, IFI44, IFI44L, MX1, IFI27, OAS1 RSAD2 gene evaluated by RT-PCR whole blood. Normalized levels (Z-scores) averaged into global signature (IFN score). Differences measured Kruskal-Wallis tests, associations studied cluster, correspondence network analyses. Results An overall noted across subsets, but certain differences genes. Some already upregulated aPL-positive group compared HC (IFI44, RSAD2, all p<0.050), while others only increased (IFI6). MX1 differed SAPS, whereas IFI27 showed PAPS SAPS. composite score revealed quantitative being elevated carriers/PAPS groups HCs (both p<0.050) increasing SAPS (p<0.010) (p<0.001). Network analyses (Figure 1A) qualitative gene-gene correlation networks: (i) weaker structures found carriers, stronger higher-degree networks SLE; (ii) influence each node groups. Unsupervised cluster analysis 3 clusters 1B), whose usage thus correlating clinical status 1C). (n=51) hallmarked (p=0.032) attributed (IFI6, IFI44L IFI27; those Gene-gene interactions also 1D). Individuals more likely use III (p=0.042) 1E). Conclusion common hallmark individuals well , unique ISG has been observed. Qualitative spectrum can be identified, leading identification distinct signatures value beyond traditional categorization. Reference [1]Sciascia S, et al. Rheumatology (Oxford) (2021); 2. Miyakis J Thromb Haemost (2006); 3. Aringer M, Arthritis Rheumatol (2019) Figure 1. Acknowledgements: NIL. Disclosure Interests None Declared.