Castañeda-Delgado Julio E, Bastián-Hernandez Yadira, Macias-Segura Noe, Santiago-Algarra David, Castillo-Ortiz Jose D, Alemán-Navarro Ana L, Martínez-Tejada Pedro, Enciso-Moreno Leonor, Garcia-De Lira Yolanda, Olguín-Calderón Diana, Trouw Leendert A, Ramos-Remus Cesar, Enciso-Moreno Jose A
Medical research Unit of Zacatecas, Mexican Institute of Social Security, UIMZ-IMSS, Zacatecas, Mexico; National Council of Science and Technology, CONACYT, Catedras-CONACYT, Zacatecas, Mexico.
Medical research Unit of Zacatecas, Mexican Institute of Social Security, UIMZ-IMSS, Zacatecas, Mexico; Departamento de fisiología y farmacología, centro de ciencias básicas, Universidad Autónoma de Aguascalientes, Aguascalientes, Aguascalientes, Mexico.
Front Immunol. 2017 Mar 20;8:285. doi: 10.3389/fimmu.2017.00285. eCollection 2017.
Rheumatoid arthritis (RA) is an inflammatory debilitating disease that affects the joints in the early and productive phases of an individual's life. Several cytokines have been linked to the disease pathogenesis and are known to contribute to the inflammatory state characteristic of RA. The participation of type I interferon (IFN) in the pathogenesis of the disease has been already described as well as the identity of the genes that are regulated by this molecule, which are collectively known as the type I IFN signature. These genes have several functions associated with apoptosis, transcriptional regulation, protein degradation, Th2 cell induction, B cell proliferation, etc. This article evaluated the expression of several genes of the IFN signature in different stages of disease and their correlation with the levels of anticitrullinated protein antibodies (ACPA) anticarbamylated protein (Anti-CarP) antibodies.
Samples from individuals with early and established RA, high-risk individuals (ACPA+ and ACPA-), and healthy controls were recruited at "Unidad de Artritis y Rheumatismo" (Rheumatism and Arthritis Unit) in Guadalajara Jalisco Mexico. Determinations of ACPA were made with Eurodiagnostica ACPA plus kit. Anti-CarP determinations were made according to previously described protocols. RNA was isolated, and purity and integrity were determined according to RNA integrity number >6. Gene expression analysis was made by RT-qPCR using specific primers for mRNAs of the type I IFN signature. Relative gene expression was calculated according to Livak and Schmitgen.
Significant differences in gene expression were identified when comparing the different groups for and ( < 0.05), also when comparing established RA and ACPA- in both IFIT 1 and . An increased expression of was identified ( < 0.05), and a clear tendency toward increase was identified for . , and were found to be elevated in the chronic/established RA and early RA ( < 0.05). Significant correlations were identified for the IFN signature genes with the levels of ACPA and anti-CarP ( < 0.05).
Our data confirm previous observations in the role of IFN signature and the pathogenesis of RA. Also, we provide evidence of an association between several genes of the IFN signature (that regulate Th2 cells and B cell proliferation) with the levels of anti-CarP antibodies and ACPA.
类风湿关节炎（RA）是一种炎症性致残疾病，在个体生命的早期和活动期影响关节。几种细胞因子与该疾病的发病机制有关，并且已知它们会导致RA的炎症状态。I型干扰素（IFN）在该疾病发病机制中的参与以及受该分子调控的基因的身份已经被描述，这些基因统称为I型IFN特征。这些基因具有与细胞凋亡、转录调控、蛋白质降解、Th2细胞诱导、B细胞增殖等相关的多种功能。本文评估了IFN特征的几个基因在疾病不同阶段的表达及其与抗瓜氨酸化蛋白抗体（ACPA）、抗氨甲酰化蛋白（Anti-CarP）抗体水平的相关性。
从墨西哥哈利斯科州瓜达拉哈拉的“关节炎与风湿病科”招募了早期和确诊的RA患者、高危个体（ACPA阳性和ACPA阴性）以及健康对照的样本。使用Eurodiagnostica ACPA plus试剂盒测定ACPA。根据先前描述的方案进行Anti-CarP测定。分离RNA，并根据RNA完整性数值>6测定其纯度和完整性。使用I型IFN特征mRNA的特异性引物通过RT-qPCR进行基因表达分析。根据Livak和Schmitgen计算相对基因表达。
在比较不同组的 和 时（ < 0.05），以及在比较确诊的RA和ACPA阴性组的IFIT 1和 时，发现基因表达存在显著差异。发现 的表达增加（ < 0.05），并且 有明显的增加趋势。在慢性/确诊的RA和早期RA中发现 、 和 升高（ < 0.05）。发现IFN特征基因与ACPA和Anti-CarP水平存在显著相关性（ < 0.05）。
我们的数据证实了先前关于IFN特征在RA发病机制中的作用的观察结果。此外，我们提供了证据表明IFN特征的几个基因（调节Th2细胞和B细胞增殖）与Anti-CarP抗体和ACPA水平之间存在关联。
