Unidad de Investigación Biomédica de Zacatecas, IMSS, Zacatecas, México.
Facultad de Medicina, Departamento de Inmunología, Universidad Autónoma de San Luis Potosí, San Luis Potosí, México.
Int J Immunogenet. 2019 Apr;46(2):59-66. doi: 10.1111/iji.12414. Epub 2019 Jan 25.
Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by chronic and symmetrical inflammation of synovial tissue with subsequent joint destruction. SUMO1 is an important regulator of apoptosis through non-canonical mechanism in synovial fibroblasts, and POU2AF1 is a known B-cell transcriptional co-activator. The specific objective of this study was to measure the expression of SUMO1 and POU2AF1 on first-degree relatives of patients with RA and also in the preclinical and clinical stages of RA and describe their possible role in RA physiopathology. Blood samples were collected from ACPA+, ACPA-, early and established RA subjects recruited. ACPAs and CarP autoantibodies were determined by ELISA Eurodiagnostica CCplus kit according to previously described protocols. RNA was isolated from blood samples; the purity as integrity was determined. Gene expression analysis was made by RT-qPCR using specific primers for SUMO1 and POU2AF1 mRNAs; relative expression was determined according to the 2 method procedure. Significant differences in the expression of both, SUMO1 and POU2AF1 were identified when comparing arthritis versus healthy or ACPA+ individuals, suggesting that the down regulation of such genes starts after the onset of symptoms in RA patients. Also, a significant correlation was identified for POU2AF1 and disease progression whit a downward trend for those with established RA. The implications of such gene down regulation are discussed in the context of RA physiopathology.
类风湿关节炎（RA）是一种系统性自身免疫性疾病，其特征为滑膜组织的慢性和对称性炎症，随后发生关节破坏。SUMO1 是通过滑膜成纤维细胞中非经典机制调节细胞凋亡的重要调节剂，POU2AF1 是已知的 B 细胞转录共激活因子。本研究的具体目的是测量 RA 患者一级亲属以及 RA 的临床前和临床阶段中 SUMO1 和 POU2AF1 的表达，并描述它们在 RA 病理生理学中的可能作用。从 ACPA+、ACPA-、早期和确诊 RA 患者中采集血样。根据先前描述的方案，通过 ELISA Eurodiagnostica CCplus 试剂盒测定 ACPAs 和 CarP 自身抗体。从血样中分离 RNA；根据纯度和完整性进行测定。通过 RT-qPCR 用 SUMO1 和 POU2AF1 mRNAs 的特异性引物进行基因表达分析；根据 2 法程序确定相对表达。当比较关节炎与健康或 ACPA+个体时，发现 SUMO1 和 POU2AF1 的表达均存在显著差异，这表明这些基因的下调在 RA 患者出现症状后开始。此外，还发现 POU2AF1 与疾病进展之间存在显著相关性，在确诊 RA 患者中呈下降趋势。讨论了这种基因下调在 RA 病理生理学中的意义。
