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Evaluation of SUMO1 and POU2AF1 in whole blood from rheumatoid arthritis patients and at risk relatives

机译:从类风湿性关节炎患者和风险亲属的全血中的SUMO1和POU2AF1评估

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Abstract 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 ‐ΔΔct 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.
机译:摘要类风湿性关节炎(RA)是一种全身自身免疫疾病,其特征在于滑膜组织与随后的关节破坏的慢性和对称炎症。 SUMO1是通过在滑膜成纤维细胞中的非规范机制通过非规范机制的重要调节因子,并且POU2AF1是已知的B细胞转录共活化剂。本研究的具体目的是测量SUMO1和POU2AF1在RA患者的一级亲属和RA的临床前和临床阶段的表达,并描述其在RA Physiopathology中的作用。从ACPA +,ACPA,早期和建立的RA受试者收集血液样品。根据先前描述的协议,由ELISA Eurodiagnostica CCPlus套件确定ACPA和鲤鱼自身抗体。从血液样品中分离RNA;确定了纯度的纯度。基因表达分析通过RT-QPCR使用SuMO1和POU2AF1 MRNA的特异性引物进行;根据2-ΔΔCT方法程序确定相对表达。在比较关节炎与健康或ACPA +个体的情况下,鉴定了SumO1和POU2AF1表达的显着差异,这表明这种基因的下调在RA患者的症状发作后开始调节。此外,鉴定了POU2AF1的显着相关性,并且疾病进展均为已建立RA的疾病的下行趋势。在RA Physiopathology的背景下讨论了这种基因下调调节的影响。

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