Abstract
Autoimmune diseases involve a complex dysregulation of immunity. Autoimmune diseases include many members [e.g., rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE)], and most of them are classified according to what organs and tissues are targeted by the damaging immune response. Many studies have focused on finding specific biomarkers for single autoimmune diseases, but so far, there are no universal biomarkers for detecting almost all autoimmune diseases. Serum miRNAs have served as potential biomarkers for detecting various diseases. The purpose of this study was to find a universal biomarker for diagnosing autoimmune diseases. Regulatory T cells (Tregs) play a crucial role in protecting an individual from autoimmunity, and depletion of Tregs in mice is considered a representative animal model of autoimmune disease. Two mouse models for Treg depletion, in which Treg was depleted by CD25mAb (in C57 mice) or by diphtheria toxin (DT) (in Foxp3DTR mice), were investigated, and 381 miRNAs were identified in the serum of mice with Treg depletion. A distinctive circulating miRNA profile was identified in Treg-depleted mice and in patients with autoimmune disease. QRT-PCR confirmation and ROC curve analysis determined that six miRNAs (miR-551b, miR-448, miR-9, miR-124, miR-148, and miR-34c) in the Treg-depleted mouse models and three miRNAs [miR-551b (specificity 73.5%, sensitivity 88.4%), miR-448 (specificity 82.4%, sensitivity 91.3%), and miR-124 (specificity 76.5%, sensitivity 91.3%)] in patients with RA, SLE, Sjogren's syndrome (SS), and ulcerative colitis (UC) could serve as valuable specific biomarkers. These circulating miRNAs may represent potential universal biomarkers for autoimmune diseases diagnosis and prognosis.
Highlights
Autoimmune diseases reflect the interplay between environment and genetic factors [1,2,3]
C57BL/6 mice and Foxp3DTR mice were injected with CD25 mAb or diphtheria toxin (DT) to eliminate CD4+ CD25+ Forkhead box P3 (Foxp3)+ Tregs
The levels of inflammatory cytokines TNF-α, IL-6, and IFNγ were dramatically increased in serum from mice with Treg depletion compared to the mice without Treg depletion (Figure 1E), indicating that elimination of CD4+ CD25+ Foxp3+ Tregs is sufficient to disrupt immunological balance
Summary
Autoimmune diseases reflect the interplay between environment and genetic factors [1,2,3]. The diseases share a substantial degree of immunopathology, including increased secretion of inflammatory cytokines by autoreactive CD4+ T cells and a loss of Regulatory T cells (Tregs) function [4, 5]. Most autoimmune diseases are classified based on which organs and tissues are targeted by the damaging immune response [e.g., primary biliary cirrhosis [6], type 1 diabetes mellitus [1], arthritis [7], and myositis [8]]. Autoimmune diseases include many types, and there is. Serum microRNA as Biomarkers of Autoimmune Diseases an autoimmune disease specific to nearly every organ in the body [8]. Specific diagnostic methods are used for each autoimmune disease, which is tedious and costly. It is urgent to find a universal marker to diagnose autoimmune diseases, which will provide new possibilities for autoimmune disease detection and treatment
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