Circulating microRNAs as biomarkers of disease and typification of the atherothrombotic status in antiphospholipid syndrome
Carlos Pérez-Sánchez,
Iván Arias-de la Rosa,
María Ángeles Aguirre,
María Luque-Tévar,
Patricia Ruiz-Limón,
Nuria Barbarroja,
Yolanda Jiménez-Gómez,
María Carmen Ábalos-Aguilera,
Eduardo Collantes-Estévez,
Pedro Segui,
Francisco Velasco,
María Teresa Herranz,
Jesús Lozano-Herrero,
María Julia Hernandez-Vidal,
Constantino Martínez,
Rocío González-Conejero,
Massimo Radin,
Savino Sciascia,
Irene Cecchi,
María José Cuadrado,
Chary López-Pedrera
Affiliations
Carlos Pérez-Sánchez
Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Spain
Iván Arias-de la Rosa
Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Spain
María Ángeles Aguirre
Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Spain;Unidad de Gestión Clínica Reumatología, Hospital Universitario Reina Sofía, Córdoba, Spain
María Luque-Tévar
Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Spain
Patricia Ruiz-Limón
Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Spain
Nuria Barbarroja
Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Spain
Yolanda Jiménez-Gómez
Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Spain
María Carmen Ábalos-Aguilera
Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Spain
Eduardo Collantes-Estévez
Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Spain;Unidad de Gestión Clínica Reumatología, Hospital Universitario Reina Sofía, Córdoba, Spain;Departamento de Medicina (Medicina, Dermatología y Otorrinolaringología), Universidad de Córdoba, Spain
Pedro Segui
Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Spain;Unidad de Gestión Clínica Radiología, Hospital Universitario Reina Sofía, Córdoba, Spain
Servicio de Medicina Interna, Hospital Morales Meseguer, Murcia, Spain
Jesús Lozano-Herrero
Servicio de Medicina Interna, Hospital Morales Meseguer, Murcia, Spain
María Julia Hernandez-Vidal
Servicio de Medicina Interna, Hospital Morales Meseguer, Murcia, Spain
Constantino Martínez
Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, Spain
Rocío González-Conejero
Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, Spain
Massimo Radin
Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases, Torino, Italy
Savino Sciascia
Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases, Torino, Italy
Irene Cecchi
Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases, Torino, Italy
María José Cuadrado
Lupus Research Unit and St. Thomas’ Hospital, London, UK
Chary López-Pedrera
Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Spain;Unidad de Gestión Clínica Reumatología, Hospital Universitario Reina Sofía, Córdoba, Spain
We aimed to identify the plasma miRNA profile of antiphospholipid syndrome (APS) patients and to investigate the potential role of specific circulating miRNAs as non-invasive disease biomarkers. Ninety APS patients and 42 healthy donors were recruited. Profiling of miRNAs by PCR-array in plasma of APS patients identified a set of miRNAs differentially expressed and collectively involved in clinical features. Logistic regression and ROC analysis identified a signature of 10 miRNA ratios as biomarkers of disease. In addition, miRNA signature was related to fetal loss, atherosclerosis, and type of thrombosis, and correlated with parameters linked to inflammation, thrombosis, and autoimmunity. Hard clustering analysis differentiated 3 clusters representing different thrombotic risk profile groups. Significant differences between groups for several miRNA ratios were found. Moreover, miRNA signature remained stable over time, demonstrated by their analysis three months after the first sample collection. Parallel analysis in two additional cohorts of patients, including thrombosis without autoimmune disease, and systemic lupus erythematosus without antiphospholipid antibodies, each displayed specific miRNA profiles that were distinct from those of APS patients. In vitro, antiphospholipid antibodies of IgG isotype promoted deregulation in selected miRNAs and their potential atherothrombotic protein targets in monocytes and endothelial cells. Taken together, differentially expressed circulating miRNAs in APS patients, modulated at least partially by antiphospholipid antibodies of IgG isotype, might have the potential to serve as novel biomarkers of disease features and to typify patients’ atherothrombotic status, thus constituting a useful tool in the management of the disease.