Dysregulation of lncRNAs in autoimmune neuropathies

Abstract

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Guillain-Barré syndrome (GBS) are inflammatory neuropathies with different clinical courses but similar underlying mechanisms. Long non-coding RNAs (lncRNAs) might affect pathogenesis of these conditions. In the current project, we have selected HULC, PVT1, MEG3, SPRY4-IT1, LINC-ROR and DSCAM-AS1 lncRNAs to appraise their transcript levels in the circulation of CIDP and GBS cases versus controls. Expression of HULC was higher in CIDP patients compared with healthy persons (Ratio of mean expression (RME) = 7.62, SE = 0.72, P < 0.001). While expression of this lncRNA was not different between female CIDP cases and female controls, its expression was higher in male CIDP cases compared with male controls (RME = 13.50, SE = 0.98, P < 0.001). Similarly, expression of HULC was higher in total GBS cases compared with healthy persons (RME = 4.57, SE = 0.65, P < 0.001) and in male cases compared with male controls (RME = 5.48, SE = 0.82, P < 0.001). Similar pattern of expression was detected between total cases and total controls. PVT1 was up-regulated in CIDP cases compared with controls (RME = 3.04, SE = 0.51, P < 0.001) and in both male and female CIDP cases compared with sex-matched controls. Similarly, PVT1 was up-regulated in GBS cases compared with controls (RME = 2.99, SE = 0.55, P vale < 0.001) and in total patients compared with total controls (RME = 3.02, SE = 0.43, P < 0.001). Expression levels of DSCAM-AS1 and SPRY4-IT1 were higher in CIDP and GBS cases compared with healthy subjects and in both sexes compared with gender-matched healthy persons. Although LINC-ROR was up-regulated in total CIDP and total GBS cases compared with controls, in sex-based comparisons, it was only up-regulated in male CIDP cases compared with male controls (RME = 3.06, P = 0.03). Finally, expression of MEG3 was up-regulated in all subgroups of patients versus controls except for male GBS controls. SPRY4-IT could differentiate CIDP cases from controls with AUC = 0.84, sensitivity = 0.63 and specificity = 0.97. AUC values of DSCAM-AS1, MEG3, HULC, PVT1 and LINC-ROR were 0.80, 0.75, 0.74, 0.73 and 0.72, respectively. In differentiation between GBS cases and controls, SPRY4-IT and DSCAM-AS1 has the AUC value of 0.8. None of lncRNAs could appropriately differentiate between CIDP and GBS cases. Combination of all lncRNAs could not significantly enhance the diagnostic power. Taken together, these lncRNAs might be involved in the development of CIDP or GBS.

Figure 1

Expression levels of lncRNAs in study subgroups. Mean values and interquartile range are displayed. Purple dots show each expression level. Black dot represents outliers. (This figure has been depicted by R software).

Figure 2

Correlations between expression quantities of lncRNAs among patients. (This figure has been depicted by R software).

Figure 3

Correlations between expression quantities of lncRNAs among healthy controls. (This figure has been depicted by R software).

Figure 4

ROC curves showing the diagnostic power of lncRNAs in differentiation of CIDP cases from controls (A), GBS cases from controls (B), CIDP cases from GBS cases (C), and total patients from controls (D).