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Ferrata Storti Foundation
Coagulation & its Disorders
Circulating microRNAs as biomarkers
of diseaseandtypificationofthe atherothrombotic status in antiphospholipid syndrome
Haematologica 2018 Volume 103(5):908-918
María Teresa Herranz,6 Jesús Lozano-Herrero,6 María Julia Hernandez-Vidal,6
Carlos Pérez-Sánchez,1* Iván Arias-de la Rosa,1* María Ángeles Aguirre,1,2 María Luque-Tévar,1 Patricia Ruiz-Limón,1 Nuria Barbarroja,1
Yolanda Jiménez-Gómez,1 María Carmen Ábalos-Aguilera,1
Eduardo Collantes-Estévez,1,2,3 Pedro Segui,1,4 Francisco Velasco,5
778 Constantino Martínez, Rocío González-Conejero, Massimo Radin,
Savino Sciascia,8 Irene Cecchi,8 María José Cuadrado9** and Chary López- Pedrera1,2**
1Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Spain; 2Unidad de Gestión Clínica Reumatología, Hospital Universitario Reina Sofía, Córdoba, Spain; 3Departamento de Medicina (Medicina, Dermatología y Otorrinolaringología), Universidad de Córdoba, Spain; 4Unidad de Gestión Clínica Radiología, Hospital Universitario Reina Sofía, Córdoba, Spain; 5Unidad de Gestión Clínica Hematología, Hospital Universitario Reina Sofía, Córdoba, Spain; 6Servicio de Medicina Interna, Hospital Morales Meseguer, Murcia, Spain; 7Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, Spain; 8Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases, Torino, Italy and 9Lupus Research Unit and St. Thomas’ Hospital, London, UK
*CP-S and IA-R shared first authorship and contributed equally to this work. **MJC and CL-P shared last author- ship and contributed equally to this work.
ABSTRACT
We aimed to identify the plasma miRNA profile of antiphospho- lipid syndrome (APS) patients and to investigate the potential role of specific circulating miRNAs as non-invasive disease bio- markers. 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 signa- ture of 10 miRNA ratios as biomarkers of disease. In addition, miRNA signature was related to fetal loss, atherosclerosis, and type of thrombo- sis, and correlated with parameters linked to inflammation, thrombosis, and autoimmunity. Hard clustering analysis differentiated 3 clusters rep- resenting 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 antiphospho- lipid 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 manage- ment of the disease.
Introduction
Antiphospholipid syndrome (APS) is a clinical disorder characterized by the occurrence of thrombosis and/or pregnancy morbidity associated with the persist- ent presence of antiphospholipid antibodies (aPL), including anti-cardiolipin anti-
Correspondence:
rosario.lopez.exts@juntadeandalucia.es
Received: November 10, 2017. Accepted: February 22, 2018. Pre-published: March 15, 2018.
doi:10.3324/haematol.2017.184416
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/103/5/908
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