Comparison of the Serum Metabolic Signatures Based on 1 H NMR between Thrombotic Antiphospholipid Syndrome (APS) Patients and Healthy Individuals

Abstract

Antiphospholipid syndrome (APS) is an acquired immuno-mediated disorder, in which antiphospholipid antibodies (aPL) against a variety of phospholipids and phospholipid transport proteins are persistently produced. aPL include a heterogeneous group of circulating immunoglobulins: lupus anticoagulant (LA), anticardiolipin antibodies (aCL) and anti-β2glycoprotein-I (anti-β2GPI). Their presence is related to diverse clinical phenomena including arterial and venous thrombosis, which can be related to different pathogenic properties, such as its effect on the clotting pathways, endothelium and platelets. Metabolomic can be useful improving diagnosis, prognostic and therapeutic interventions, in vascular disease (Kirlikaya B. et al, 2019) The aim of this study was to identify metabolic alterations in patients with thrombotic APS characterized by deep venous thrombosis (DVT) compared to healthy individuals using liquid-state 1H-NMR data acquisition combined with chemometrics analysis. We evaluated ten serum samples of patients with APS (mean age 39 years; 6 female/4 male), who attended at the outpatient clinic of Hemocentro of Campinas, Unicamp-Brazil, from 2013 to 2017 (Table 1). The exclusion criteria were the presence of cancer and renal disease, smoking and alcoholism. The samples were collected up to 2 years the last thrombotic episode. All patients except one (suprahepatic vein) suffered DVT of the lower limbs and only two of them presented 2 thrombotic episodes. Six patients were classified as primary APS and four with secondary (three presented systemic lupus erythematosus (SLE) and one were diagnosed with psoriasis). All patients with secondary APS were using immunosuppressive drugs: prednisone and azathioprine, or methotrexate. None of the patients were triple positive. The control group were healthy individuals (mean age 41 years; 5 female/5male), from staff of the Hemocentro and the exclusion criteria were the same as for patients. Multivariate analysis pointed to slight differential metabolic profiles among APS and controls, and between primary and secondary APS. Different metabolites associated to energy metabolism, such as increased glucose consumption and lactate production, as well as differences at spectral regions corresponding to some aromatic amino acids were identified in APS group when compared to controls. Our results are promising, such as different profiles could be observed, both regarding patients vs. controls, such as primary vs. secondary APS. The use of immunosuppressive drugs in secondary APS may contribute to these changes. Although questions regarding the translatability of metabolomics findings into clinical practice, our results showed the high sensitivity and specificity of NMR spectroscopy to distinguish healthy and APS. To have a better understanding of the metabolic alterations potentially involved in the APS, additional analyses including mean spectra are being made. Disclosures No relevant conflicts of interest to declare.