Martínez-Hernández Rebeca, Fuente Hortensia de la, Lamana Amalia, Sampedro-Núñez Miguel, Ramos-Levi Ana, Serrano-Somavilla Ana, García-Vicuña Rosario, Ortiz Ana M, Daudén Esteban, Llamas-Velasco Mar, Chicharro Pablo, Rodríguez-Jiménez Pedro, Sanz-García Ancor, Sánchez-Madrid Francisco, González-Álvaro Isidoro, Marazuela Mónica
Department of Endocrinology, Hospital Universitario de La Princesa, Instituto de Investigación Princesa, Universidad Autónoma de Madrid, C/ Diego de León 62, 28006, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER GCV14/ER/12), Spain.
Department of Immunology, Hospital Universitario de La Princesa, Instituto de Investigación Princesa, Universidad Autónoma de Madrid, C/ Diego de León 62, 28006, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Spain.
J Autoimmun. 2020 Jul;111:102472. doi: 10.1016/j.jaut.2020.102472. Epub 2020 May 5.
Immune-mediated inflammatory disorders (IMID) are a group of diseases that present inflammation as a major pathogenic mechanism. They affect 15% of the population and pose a heavy socio-economic burden. Despite the growing knowledge on the etiopathogenesis of these diseases and the marked improvement in their management, there is a lack of predictive markers of IMID development or severity suitable for early diagnosis and adjustment of treatment intensity. The possibility that certain circulating miRNA profiles could be used as biomarkers of risk of development and/or severity of several autoimmune diseases has fuelled the interest in using them to improve the selection of successful treatments. The multi-pronged approach proposed here sought to reveal circulating miRNAs and miRNA signatures that could act as new predictive biomarkers of IMID development and severity. Our results showed that the circulating levels of miR-19b and miR-26b were significantly decreased (p < 0.001) in IMID patients compared to controls. Furthermore, receiver operating characteristic (ROC) curve analysis showed that these miRNAs were suitable discriminators capable to identify an IMID, with areas under the curve (AUC) of 0.85 and 0.83, respectively. In addition, we established that miR-19a and miR-143 were significantly increased in IMID patients with severe disease (p < 0.05). In summary, our findings identify two different miRNA signatures. One of them is associated with the presence of IMIDs and could lead to the development of tools for their early detection. The second signature is able to discriminate between mild and severe forms of these disorders and could be a putative tool to select patient candidates for a more intense treatment.
免疫介导的炎症性疾病(IMID)是一组以炎症为主要致病机制的疾病。它们影响着15%的人口,并带来沉重的社会经济负担。尽管对这些疾病的病因发病机制的认识不断增加,其治疗也有了显著改善,但仍缺乏适合早期诊断和调整治疗强度的IMID发生或严重程度的预测标志物。某些循环miRNA谱可能用作几种自身免疫性疾病发生风险和/或严重程度的生物标志物,这一可能性激发了人们利用它们来改进成功治疗选择的兴趣。本文提出的多管齐下方法旨在揭示可作为IMID发生和严重程度新预测生物标志物的循环miRNA和miRNA特征。我们的结果表明,与对照组相比,IMID患者中miR-19b和miR-26b的循环水平显著降低(p<0.001)。此外,受试者工作特征(ROC)曲线分析表明,这些miRNA是能够识别IMID的合适判别指标,曲线下面积(AUC)分别为0.85和0.83。此外,我们确定在患有严重疾病的IMID患者中miR-19a和miR-143显著增加(p<0.05)。总之,我们的研究结果确定了两种不同的miRNA特征。其中一种与IMID的存在相关,可能会促使开发早期检测工具。第二种特征能够区分这些疾病的轻度和重度形式,可能是选择更强化治疗候选患者的一种推定工具。