Attia Mohamed S, Ewida Heba A, Abdel Hafez Mohamed Aly, El-Maraghy Shohda A, El-Sawalhi Maha M
Pharmacology, Toxicology and Biochemistry Department, Faculty of Pharmacy, Future University in Egypt (FUE), Cairo 11835, Egypt.
Neurology Department, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt.
Diagnostics (Basel). 2023 Apr 17;13(8):1448. doi: 10.3390/diagnostics13081448.
Relapsing-remitting multiple sclerosis (RRMS) is the most prevalent MS subtype. Ample evidence has indicated that long noncoding RNAs (lncRNAs) are crucial players in autoimmune and inflammatory disorders. This study investigated the expression of lnc-EGFR, SNHG1, and lincRNA-Cox2 in RRMS patients during active relapses and in remission. Additionally, the expression of FOXP3, a master transcription factor for regulatory T cells, and NLRP3-inflammasome-related genes were determined. Relationships between these parameters and MS activity and annualized relapse rate (ARR) were also evaluated. The study included 100 Egyptian participants: 70 RRMS patients (35 during relapse and 35 in remission) and 30 healthy controls. RRMS patients showed significant downregulation of lnc-EGFR and FOXP3 and dramatic upregulation of SNHG1, lincRNA-Cox2, NLRP3, ASC, and caspase-1 compared to controls. Lower serum TGF-β1 and elevated IL-1β levels were observed in RRMS patients. Notably, patients during relapses displayed more significant alterations than those in remission. Lnc-EGFR was positively correlated with FOXP3 and TGF-β1 and negatively correlated with ARR, SNHG1, lincRNA-Cox2, and NLRP3 inflammasome components. Meanwhile, SNHG1 and lincRNA-Cox2 were positively correlated with ARR, NLRP3, ASC, caspase-1, and IL-1β. Excellent diagnostic performance for lnc-EGFR, FOXP3, and TGF-β1 was demonstrated, while all biomarkers exhibited strong prognostic potential for predicting relapses. Finally, the differential expression of lnc-EGFR, SNHG1, and lincRNA-Cox2 in RRMS patients, especially during relapses, suggests their involvement in RRMS pathogenesis and activity. Correlation between their expression and ARR implies relationships to disease progression. Our findings also highlight their promising roles as biomarkers for RRMS.
复发缓解型多发性硬化症(RRMS)是最常见的MS亚型。大量证据表明,长链非编码RNA(lncRNAs)在自身免疫性和炎症性疾病中起着关键作用。本研究调查了RRMS患者在疾病活动复发期和缓解期lnc-EGFR、SNHG1和lincRNA-Cox2的表达情况。此外,还测定了调节性T细胞的主要转录因子FOXP3以及NLRP3炎性小体相关基因的表达。还评估了这些参数与MS活动及年化复发率(ARR)之间的关系。该研究纳入了100名埃及参与者:70例RRMS患者(35例处于复发期,35例处于缓解期)和30名健康对照者。与对照组相比,RRMS患者lnc-EGFR和FOXP3显著下调,而SNHG1、lincRNA-Cox2、NLRP3、ASC和半胱天冬酶-1显著上调。RRMS患者血清TGF-β1水平降低,IL-1β水平升高。值得注意的是,复发期患者的变化比缓解期患者更为显著。lnc-EGFR与FOXP3和TGF-β1呈正相关,与ARR、SNHG1、lincRNA-Cox2和NLRP3炎性小体成分呈负相关。同时,SNHG1和lincRNA-Cox2与ARR、NLRP3、ASC、半胱天冬酶-1和IL-1β呈正相关。lnc-EGFR、FOXP3和TGF-β1具有出色的诊断性能,而所有生物标志物在预测复发方面均具有很强的预后潜力。最后,RRMS患者中lnc-EGFR、SNHG1和lincRNA-Cox2的差异表达,尤其是在复发期,表明它们参与了RRMS的发病机制和疾病活动。它们的表达与ARR之间的相关性暗示了与疾病进展的关系。我们的研究结果还突出了它们作为RRMS生物标志物的潜在价值。