Enhanced type I interferon signature in primary APS patients is associated with thrombocytopenia

Sophie Scholz, Eduard Nitschke, L.S. Dreveton, Annika Wiedemann, Beniam Assefa, Franziska Szelinski, E. Schrezenmeier, Axel Prüß, Gerhard Krönke, Thomas Dörner, Ana‐Luisa Stefanski

Introduction Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombotic events and/or obstetric complications due to persistent antiphospholipid antibodies. Type I interferon (IFN) upregulation has been identified as a potential contributor to the pathophysiology of APS, however, the relationship between type I IFN and clinical manifestations of APS still needs to be delineated. The objective of this study was the evaluation of the potential role of type I IFN regarding different APS manifestations. Methods We conducted a retrospective analysis of APS patients who presented to our clinic between 2017 and 2024, focusing on clinical manifestations, recurring events and serological profiles in relation to Siglec-1 expression on monocytes, as a surrogate marker of type I IFN signature. Results Out of the 218 APS patients included in the study, 123 were diagnosed with primary APS (pAPS) and 95 with secondary APS (sAPS), the latter mostly SLE associated, showing a general higher type I IFN signature as the pAPS cohort. While no significant differences in Siglec-1 expression were observed across most APS manifestations (venous, arterial, mixed and obstetric events), significantly higher type I IFN activity was detected in APS patients with thrombocytopenia compared to those without (p = 0.0061). Moreover, we found an inverse correlation between platelet numbers and Siglec-1 values. Interestingly, the difference in type I IFN signature was confirmed in the pAPS cohort with thrombocytopenia (p = 0.0242). In sAPS, Siglec-1 expression did not differ significantly between patients with and without thrombocytopenia (p = 0.4664). With regard to serological and clinical characteristics, patients with thrombocytopenia exhibited a higher prevalence of triple positivity, elevated levels of anti-cardiolipin IgG antibodies and an increased incidence of recurrent and mixed (arterial/venous) thromboembolic events. Discussion To conclude, the data indicate that type I IFN may be a relevant factor for the occurrence of thrombocytopenia in pAPS. Moreover, thrombocytopenia in APS was linked to increased prevalence of triple positivity, higher anti-cardiolipin IgG titres, and higher disease severity, underscoring the importance of closer monitoring in this subgroup. These results warrant validation in prospective studies and could support potential therapeutic targeting of type I IFN in a subset of APS patients.