Pos1135 effect of immunomodulatory therapies on antiphospholipid antibodies titers in children with antiphospholipid syndrome

Background Pediatric Antiphospolipid Syndrome (APS) is an autoimmune disease characterized by venous and/or arterial thrombotic events (TE) associated with 2 consecutive positive determinations (at least 12 weeks apart) of antiphospholipid antibodies (aPL), IgG/IgM anticardiolipin (aCL), IgG/IgM β2-glycoprotein I (aβ2GPI) and/or lupus anticoagulant (LA). Recent data suggests that aPL levels may decrease over time due to the natural history of the disease or to treatments. Therefore, monitoring of aPL levels may represent a strategy to evaluate disease activity and response to therapies. Objectives To investigate the trend over time of aPL titers in children with APS, comparing patients under immunomodulatory therapies and those without them. Methods A descriptive, observational, cross-sectional study was carried out in children with APS. aPLs testing was carried out in all patients from diagnosis every 3-4 months for 2 years. Interferon Gene Signature (IGS) was assessed as described by Crow [1] . Laboratory parameters, clinical and demographic data was retrieved and analyzed. Statistical analysis was performed with software R_v. 4.0.3. Results Sixteen children with a diagnosis of APS were included in this study. The median age at disease onset was 11.5 years (range: 6 months – 17 years) and 62.5% were female; 87.5% Caucasians. Thirteen patients (81.2%) had a diagnosis of primary APS and 3 (18.8%) out of 16 of secondary APS. Regarding clinical manifestations, 11 children developed at least one TE (7 arterial and 5 venous). Cerebral territory was the most frequently involved with 5 thrombosis, followed by 3 deep vein thrombosis, 1 pulmonary thromboembolism and 2 arterial renal thrombosis. Most of the patients received an antiaggregant and/or anticoagulant therapy (13 and 8 patients, respectively). However, 1 patient presented a new TE after the antiaggregant withdrawal. A total of 12 (75%) children developed at least one non-criterion manifestation: 7 patients (44%) cardiac (Libman-Sacks endocarditis or valvular heart disease), 7 patients (44%) neurological (chorea or white matter lesions), 6 patients (37.5%) hematological (thrombocytopenia, hemolytic anemia or Evans syndrome) and 1 patient (3.8%) a renal thrombotic microangiopathy. Related to immunological parameters, 4 (25%) were positive for only 1 aPL, 5 (42%) for 2 aPL subtypes and 7 (44%) for all 3 aPL subtypes, showing the highest rates IgG aβ2GP (87.5%) and IgG aCL (81.25%). Lower rates were identified for LA (44%), IgM aCL (18.7%) and IgM aB2GP (12.5%). Four (25%) had ANA positivity (3 secondary and 1 primary APS). Regarding treatment, 13 children (81.25%) received at least one immunomodulatory drug (13 patients mycophenolate; 4 rituximab) and 3 (18.7%) were not treated with them. During the 2-year-follow-up, 11 patients (68.8%) showed a reduction of aPL titers compared to the onset, with becoming 9 negative (56.3%) at the end of follow-up (Figure 1A). Of those who were negative, 8 children were under immunomodulatory therapies and only 1 did not receive any treatment. Five patients (31.2%) showed stable titers of aPLs during follow-up. Of them, 2 were not treated with immunomodulatory therapies and 2 were under mycophenolate but with poor compliance (reduction of titers with the restart of therapy were observed). We also evaluated the presence of the IGS in 11 patients with APS for whom a whole blood RNA sample was available: the IGS was positive in 9 (81.8%) of 11 children (7 with primary APS and 2 with secondary APS). Conclusion Our data suggest the possible effect of immunomodulatory therapies in reducing antibody titers in APS. Therefore, it may represent a strategy to control the disease activity leading to a better prognosis. Further studies are needed to confirm and expand our data. Reference [1]Rice GI, et al. Lancet Neurol 2013; 12:1159-69. Figure 1. A. Trend of IgG aB2GP during 2 years of follow-up. B. Trend of IgG aCL during 2 years of follow-up.Red line (0): children without immunomodulatory (IMM) therapies; blue line (1): children with IMM therapies. Acknowledgements: NIL. Disclosure of Interests None Declared.