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.

miR-31-5p as a Potential Circulating Biomarker and Tracer of Clinical Improvement for Chronic Inflammatory Demyelinating Polyneuropathy

“…Influencing miRNA function may contribute to a better understanding of the CIDP pathogenesis and the selection of an effective type of treatment. It is worth noting that abnormal expression of individual microRNAs may result from changes in the genome or abnormalities in their biogenesis or may be related to epigenetic factors regulating gene expression [45][46][47][48][49]. The work of Vinci et al [47] highlighted that not only structurally determined changes in miRNA expression levels but also their epigenetic regulation seemed to be important in the CIDP pathogenesis and may become future targets for the development of new therapies modulating miRNA expression through changes in the level of methylation of their genes.…”

Lnc-HULC, miR-122, and sirtulin-1 as potential diagnostic biomarkers for psoriasis and their association with the development of metabolic syndrome during the disease course

“…They found that in patients with CVD, upregulation of lnc-HULC was related to higher blood lipid levels (TG, LDL-C), inflammatory cytokines (interleukin (IL-1, IL-17A), cell adhesion molecules (VCAM-1), and Gensini score (all P < 0.05) [ 36 ]. Besides, expression of lnc-HULC was higher in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Guillain-Barré syndrome (GBS) cases compared with controls [ 37 ]. Lnc-HULC has been shown to regulate immune responses through miR-128–3p/RAC1 axis [ 38 ] which regulates a number of inflammatory pathways such as STAT3 and NF-κB [ 39 ].…”

Significant up-regulation of lncRNAs in neuromyelitis optica spectrum disorder

“…These transcripts act by binding to histone modifying complexes, transcription factors and RNA polymerase II 11 . Dysregulated expression of lncRNAs has been associated with the immunological imbalance 12 . According to the previous studies, lncRNAs play an imperative role in autoimmune diseases since they are involved in the differentiation and activity of T and B cells, macrophages and natural killer cells 13 .…”