Usefulness of miRNA-338-3p in the diagnosis of pemphigus and its correlation with disease severity

Abstract

BackgroundPemphigus is a common life-threatening, autoimmune bullous disease effecting both cutaneous and mucous membranes. Previous diagnosis of pemphigus is based on clinical presentations, histopathology, immunofluorescence and enzyme-linked immunosorbent assay. Furthermore, no laboratory parameters could be used to indicate disease severity. MicroRNAs are endogenous small RNAs, which could be used as diagnostic biomarkers for some autoimmune diseases. Previously, miR-338-3p has been proven significantly up-regulated in pemphigus patients.MethodsPemphigus patients (including pemphigus vulgaris and pemphigus foliaceus) with active lesions and with remission, patients diagnosed as bullous pemphigoid and healthy volunteers were recruited, and miR-338-3p expression level was measured using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). Active pemphigus patients accepting treatment were followed up for at least 2 weeks to investigate the expression change of miR-338-3p during treatment period. Target genes of miR-338-3p were screened through computer-aided algorithm and verified by RT-qPCR, Western blot and Luciferase activity assay.ResultsMiR-338-3p was specifically increased in patients diagnosed as pemphigus with active lesions. The expression level of miR-338-3p gradually decreased after effective treatment. MiR-338-3p expression was independently correlated with disease severity defined by PDAI (Pemphigus Disease Area Index) or ABSIS (Autoimmune Bullous Skin Disorder Intensity Score) criteria. Up-regulation of miR-338-3p could significantly suppress RNF114 expression at mRNA and protein level in vitro.DiscussionMiR-338-3p could be used as a diagnostic biomarker of pemphigus in addition to other traditional methods. Up-regulation of MiR-338-3p was associated with more severe condition in pemphigus. RNF114 is the target gene of miR-338-3p, which probably participates in the regulation of disease activity of pemphigus.

Investigating expression pattern of eight immune‐related genes in pemphigus patients compared with the healthy controls and after rituximab therapy: Potential roles of CTLA4 and FCGR3A genes expression in outcomes of rituximab therapy

“…Also, several studies have demonstrated the differences between sera cytokines levels of pemphigus patients and healthy controls (systematically reviewed by Tavakolpour et al 9 ), while there are limited reports regarding different genes' expression profile in comparison with healthy controls. The expression of NLRP1 , 10 IPAF , 10 CD19 genes, 11 and some miRNAs including miR‐424‐5p 12 and miRNA‐338‐3p 13 were demonstrated to be significantly increased in blood samples of PV and/or PF patients. Moreover, overexpression of IL17 and IL23 genes were reported to be occurred in lesion biopsy samples of pemphigus patients 14 .…”

The long noncoding RNA MALAT‐1 functions as a competing endogenous RNA to regulate MSL2 expression by sponging miR‐338‐3p in myasthenia gravis

“…44 However, miR-338-3p is also overexpressed in various autoimmune diseases such as amyotrophic lateral sclerosis 45 and celiac disease. 47 Inspired by this experiment, we can further observe the expression level of miR-338-3p in MG patients after receiving the treatment. This suggested a direct association between MALAT-1 and miR-338-3p.…”

Exploring RNAs Interactions and Polymorphisms in the Pathophysiology of Pemphigus: A Review

“…It was shown that the severity of pemphigus is related to the level of miR-338-3p. No difference was observed between people with pemphigus for the first time and people who had relapsed disease (19).…”