Immunome Research
Open Access
ISSN: 1745-7580
+44-77-2385-9429
ISSN: 1745-7580
+44-77-2385-9429
Guillermina Girardi
King�s College London, UK
Posters & Accepted Abstracts: Immunome Res
Women with antiphospholipid syndrome (APS) have a higher incidence of abnormal pregnancy outcomes. We used mouse models of obstetric APS (OAPS) to investigate the mechanisms responsible for adverse pregnancy outcomes and the identification of targets for therapy. Using 111In-labeled aPL and single photon emission computed tomography (SPECT/ CT), we identified the placenta and the fetal brain as the main organ targets in OAPS in mice. We previously demonstrated that complement activation plays a crucial role in adverse pregnancy outcomes in OAPS. Using a novel non-invasive MRI-based method, we detected complement activation (CA) in the placenta and fetal brain in vivo in utero using anti-complement C3 antibodies labeled with nanoparticles. Placental C3 deposition was associated with placental insufficiency characterized by increased oxidative stress, angiogenic imbalance and intrauterine growth restriction. Fetal brain C3 deposition was associated with cortical axonal cytoarchitecture disruption and increased neurodegeneration. Proton MRI spectroscopy (1HMRS) showed abnormal metabolic in placentas and fetal brains from OAPS-mice compared to control mice. Antithrombotic therapy, current treatment for OAPS, fails in many patients raising the need of other therapies to improve obstetrical outcome. Hydroxychloroquine (HCQ) is increasingly used to treat OAPS; however its mechanism is unknown. HCQ prevented fetal death and the placental and fetal brain metabolic changes in OAPS-mice. The SPECT/CT studies demonstrated that HCQ does not inhibit aPL binding to tissues as was previously suggested. HCQ inhibited CA and prevented fetal brain and placental abnormalities. Diminished CA was observed in serum samples from OAPS-patients and OAPS-mice after treatment with HCQ. Promising translational studies in women with OAPS treated with statins will also be presented.