The Serum Cell-Free microRNA Expression Profile in MCTD, SLE, SSc, and RA Patients.

Barbara Stypinska,Anna Wajda,Marcela Walczyk,Ewa Walczuk,Marzena Olesinska,Aleksandra Lewandowska,Agnieszka Paradowska-Gorycka

doi:10.3390/jcm9010161

Abstract

Mixed connective tissue disease (MCTD) is a rare disorder characterized by symptoms that overlap two or more Autoimmune Connective Tissue Diseases (ACTDs). The aim of this study was to determine whether miRNAs participating in the TLRs signaling pathway could serve as biomarkers differentiating MCTD or other ACTD entities from a healthy control group and between groups of patients. Although the selected miRNA expression level was not significantly different between MCTD and control, we observed that miR-126 distinguishes MCTD patients from all other ACTD groups. The expression level of miRNAs was significantly higher in the serum of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients compared to controls. The miR-145 and -181a levels distinguished RA from other ACDT patients. miR-155 was specific for SLE patients. MiR-132, miR-143, and miR-29a distinguished RA and SLE patients from the systemic sclerosis (SSc) group. Additionally, some clinical parameters were significantly related to the miRNA expression profile in the SLE group. SLE and RA are characterized by a specific serum expression profile of the microRNAs associated with the Toll-like receptors (TLRs) signaling pathway. The analysis showed that their level distinguishes these groups from the control and from other ACTD patients. The present study did not reveal a good biomarker for MCTD patients.

Highlights

Autoimmune Connective Tissue Diseases (ACTDs) are autoimmune diseases characterized by spontaneous stimulation of the immune system and the production of antibodies against its own components of the nucleus and cytoplasm
Its level was significantly downregulated in comparison to other ACTD patients, we have not observed statistically significant differences between mixed connective tissue disease (MCTD) patients and healthy subjects. miR-126 is present within the EGFL7 gene and according to Liakouli et al (2019), it may be involved in the pathogenesis of systemic sclerosis (SSc) vasculopathy and fibrosis. miR-126 is a negative regulator of EGFL7 [24]
Our research has shown that the levels of circulating microRNAs associated with the U1-RNP/Toll-like receptors (TLRs)/IFNs signaling pathway may be not a good diagnostic marker for MCTD in particular

Summary

Introduction

Autoimmune Connective Tissue Diseases (ACTDs) are autoimmune diseases characterized by spontaneous stimulation of the immune system and the production of antibodies against its own components of the nucleus and cytoplasm (proteins or nucleic acids). There has been significant progress in understanding the pathogenesis of MCTD and the central pathogenetic role of autoantibodies against the U1- small nuclear ribonucleoprotein antigen (anti-U1-RNP) autoantibodies has clearly emerged. These antibodies are present in almost all MCTD patients, and in 30–40% of SLE patients [4,5]. Long-term studies on MCTD patients prove that the presence of anti-U1 autoantibodies correlates with the activity of the disease, with the presence of the Raynaud’s phenomenon, and with lung injury. It was suggested that these autoantibodies may interact via Toll-like receptors (TLRs) signaling and that they are closely related to the production of IFN-1 [4]

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