POS0200 TYPE I INTERFERON ACTIVITY IN PERSISTENTLY ANTIPHOSPHOLIPID ANTIBODY-POSITIVE PATIENTS WITH OR WITHOUT LUPUS: RESULTS FROM ANTIPHOSPHOLIPID SYNDROME ALLIANCE FOR CLINICAL TRIALS AND INTERNATIONAL NETWORKING (APS ACTION) CLINICAL DATABASE AND REPOSITORY (“REGISTRY”)

Background: Antiphospholipid Syndrome (APS) can occur as a primary condition or in association with Systemic Lupus Erythematosus (SLE). Proinflammatory pathways are involved in antiphospholipid antibody (aPL)-related events, which explains why antithrombotic treatment alone might not be sufficient for the management of selected aPL-positive patients. Type I Interferon (IFN-I) is implicated in the initiation, progression, and treatment response of many systemic autoimmune disorders including SLE. There is growing evidence that the interferon pathway also plays a role in the pathogenesis of APS. Gene expression profiling studies have suggested a potential role of IFN-I in differentiating the subsets of APS patients with autoimmune manifestations [1, 2]. Objectives: Our primary objective was to compare the IFN-I activity between three groups of persistently aPL-positive patients with: a) no concomitant systemic autoimmune rheumatic diseases (SARDs); b) SLE classification; and c) SLE-like disease without SLE classification. Methods: APS ACTION is an international multicenter registry of patients with persistently positive aPL, with or without additional SARDs. Baseline demographic information, aPL-related clinical events, medications, and aPL test results as well as blood samples are collected at registry entry and updated every 12 months. We compared IFN-I activity, in the first available serum or plasma sample, between three groups of persistently aPL-positive patients (with/without APS classification) with: a) no SARDs; b) SLE based on four or more 1997 ACR SLE classification criteria; and c) SLE- like disease defined as 3/11 1997 ACR SLE criteria including aPL. A sensitive and reproducible reporter cell (WISH cells) assay was used to measure the ability of sera to cause IFN-induced gene transcription to generate an IFN-I score. Three IFN-I inducible genes were selected (MX-1, IFIT-1, EIF2AK2). A cut off point of 2 standard deviations (SD) above the mean of 105 healthy controls was used to categorize IFN-I score into high vs. low. The clinical, laboratory characteristics and the IFN-I activity score of the three groups (with no SARDs, with SLE, with SLE-like disease) were compared using Kruskal-Wallis H, Chi-squared and Fisher Exact tests, followed by post hoc tests with Holm–Bonferroni correction. All statistical analyses were performed in R and RStudio (version 2024.04.1). The significance level was set at 0.05. Results: Of 1,206 patients who were part of the registry as of 2/2/24, 425 from North American Centers were identified. We excluded 36 participants: 18 with SARDs other than SLE, 12 recent recruitments with no available samples, and 6 with an indeterminate IFN-I activity score. We included 389 patients in the final analysis: 163 (42%) with no SARDs, 181 (46%) with SLE, and 45 (12%) with SLE-like disease as described above. The baseline demographic, clinical and aPL characteristics are shown in Table 1; the mean age at registry entry was 45 with female (74%) and white (78%) predominance. There were significantly more triple aPL-positive patients in the SLE-like disease group (62%) compared to patients with SLE (33%) (p-value=0.002). There were significantly more LA only patients in the SLE group (28%) compared to patients in the no SARDs group (17%) (p-value=0.037) or patients in the with SLE-like disease group (7%) (p-value=0.016). Around 30% of patients in each group had a high IFN-I activity score (defined as IFN-I activity score of ≥2); the distribution of patients with high IFN-I activity was similar between the three groups (p-value=0.801) (Table 2). Conclusion: To our knowledge, this is the largest study to date looking at the association between IFN-I and aPL using a functional assay reflective of the extent to which the IFN-I pathway is activated. We found that one-third of persistently aPL-positive patients had high IFN-I activity score, irrespective of SLE classification or "SLE-like disease". The percentage of high IFN-I activity score among aPL-positive patients without SLE is striking considering conflicting literature on the association of aPL and IFN-I activation. Multivariable analyses are underway to examine the association of IFN-I and APS clinical phenotype as well as the detailed aPL profile in this well-characterized group of patients. REFERENCES: [1] Palli et al. Type I Interferon Signature in Primary Antiphospholipid Syndrome: Clinical and Laboratory Associations. Front Immunol. 2019;10:487. [2] Verrou et al. Whole blood transcriptome identifies interferon-regulated genes as key drivers in thrombotic primary antiphospholipid syndrome. J Autoimmun. 2023;134:102978. Acknowledgements: NIL . Disclosure of Interests: None declared . © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.