Expression Of LncRNA In T Cells Of RA Patients And Its Correlation With TNF-α

BackgroundLong noncoding RNA(lncRNA)is a group of noncoding RNA with over 200nucleotides in length but without the function of encoding proteins.Its finding provide new research ideas for gene regulation in different biological contexts.LncRNA plays a crucial role in the regulation of gene expression via affecting the processes of transcriptional and post-transcriptional,protein translational,apoptosis as well as intracellular transport.Compelling evidence showing the importance of lncRNA in the pathogenesis of autoimmune diseases like rheumatoid arthritis(RA),systemic lupus erythematosus(SLE)is emerging.Abnormal expression of multiple lncRNA in RA patients suggests that lncRNA may be involved in the pathogenesis of RA.RA is a chronic autoimmune disease characterized by progressive bone,cartilage and joint destruction.It primarily involves the whole body joints and seriously affects the daily life and work of the patients.About 1%of the global population suffer a substantial burden carried from RA.Chronicity of synovial membrane inflammation,which is caused by the continuous immune cells infiltration into the normally sparsely populated synovial compartment,is a classical symptom of RA.In this case,the complex network,consisting of effector T cells,B cells and other innate effector cells,promotes the production of pro-inflammatory cytokines including tumor necrosis factor-α(TNF-α),interleukin-6(interleukin-6,IL-6).Among these pro-inflammatory cytokines,TNF-αis an essential inflammatory cytokine to the pathogenesis of RA.ObjectiveTo detect the expression levels of lncRNA(GAS5,linc0597 and H19)in T cells of patients with RA as well as healthy controls and the relationship between the expression levels of lncRNA(GAS5,linc0597 and H19)and TNF-αlevel in plasma.MethodsA case-control study was conducted and three lncRNA(GAS5,linc0597,and H19)were selected as the target lncRNA in this study.From October 2017 to December 2018,a total of 61 RA cases and 61 controls were enrolled.Samples were collected and investigated after informed consent.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect the expression levels of GAS5,linc0597 and H19 in T cells of RA cases and healthy controls,and the expression levels of TNF-αin RA cases and healthy controls were detected by using enzyme-linked immunosorbent assay(ELISA).The relationships between the expression levels of GAS5,linc0597 and H19and the TNF-αwere also investigated.Questionnaire data were entered into Epi Data3.1 via double entry,and analyzed by using SPSS 23.0.The t-test,?~2 test,Mann-Whitney rank sum test,and Spearman rank correlation were used in data analysis.ResultsA total of 59 RA patients and 57 healthy controls were included for analysis,The results showed that the expression level of GAS5 in T cells of RA cases was lower than that of healthy control T cells,and the difference was statistically significant(Z=-2.145,P=0.032).The differences between expression levels of linc0597 and H19 in T cells of RA patients and healthy controls were not found to be statistically significant(all P>0.05).Further analysis of the correlation between the expression levels of GAS5,linc0597,H19 and laboratory indicators in RA patients,including rheumatoid factor(RF)and C-reactive protein(CRP),found no statistical correlations between GAS5,linc0597and H19 with the above indicators(all P>0.05).The correlation of GAS5,linc0597 and H19 expression levels in T cells with t28,sw28,DAS28 scores and clinical medications was analyzed.The results showed that there was no statistical correlation between the expression levels of GAS5,linc0597,H19 and the above indicators and clinical medication(all P>0.05).The plasma TNF-αconcentrations in the RA case group and the healthy control group were 206.23(184.95,260.15)pg/ml and 204.72(189.25,240.87)pg/ml,respectively.There was no significant difference between the two groups(Z=-0.140,P=0.889).Further analysis found that there were no statistically significant associations between plasma TNF-αof RA patients and laboratory indicators,disease activity,etc.(all P>0.05),The expression levels of TNF-αin different doses of glucocorticoids were different(Z=-2.053,P=0.040).The correlations between the expression levels of GAS5,linc0597,H19 in T cells and plasma TNF-αwere analyzed,whereas the results showed that the expression levels of GAS5,linc0597 and H19 were not correlated with plasma TNF-α(all P>0.05).Further analysis of the correlation between the expression levels of GAS5,linc0597 and H19 in T cells between subgroups of RA patients and plasma TNF-αconcentration,The results showed that there were no statistical correlation between the expression levels of GAS5,linc0597 and H19 and plasma TNF-αconcentrations(all P>0.05).ConclusionsThe expression level of GAS5 was down-regulated in T cells of RA patients,whereas,there was no significant difference in the expression levels of linc0597 and H19 between cases and controls.There were no statistically significant correlations between GAS5,H19,linc0597 expression levels and plasma TNF-α.GAS5 is abnormally expressed in RA patients’T cells and may be a potential biomarker for the diagnosis of RA.