Case Control Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Exp Med. Dec 20, 2023; 13(5): 102-114
Published online Dec 20, 2023. doi: 10.5493/wjem.v13.i5.102
Altered expression of miR-125a and dysregulated cytokines in systemic lupus erythematosus: Unveiling diagnostic and prognostic markers
Tagreed Qassim Alsbihawi, Mojtaba Zare Ebrahimabad, Fakhri Sadat Seyedhosseini, Homa Davoodi, Nafiseh Abdolahi, Alireza Nazari, Saeed Mohammadi, Yaghoub Yazdani
Tagreed Qassim Alsbihawi, Department of Immunology, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan 49341-74515, Iran
Mojtaba Zare Ebrahimabad, Metabolic Disorders Research Center, Golestan University of Medical Sciences, Gorgan 49341-74515, Iran
Fakhri Sadat Seyedhosseini, Yaghoub Yazdani, Laboratory Sciences Research Center, Golestan University of Medical Sciences, Gorgan 49341-74515, Iran
Homa Davoodi, Department of Immunology, Golestan University of Medical Sciences, Gorgan 4934174515, Iran
Nafiseh Abdolahi, Golestan Rheumatology Research Center, Golestan University of Medical Sciences, Gorgan 49341-74515, Iran
Alireza Nazari, Department of Surgery, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan 7717933777, Iran
Saeed Mohammadi, Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan 49341-74515, Iran
Author contributions: Alsbihawi TQ, Seyedhosseini F, Davoodi H, Mohammadi S, and Yazdani Y contributed to conceptualization (Mohammadi S and Yazdani Y), contributed to methodology; Alsbihawi TQ, Ebrahimabad MZ, and Mohammadi S contributed to software; Alsbihawi TQ, Mohammadi S, and Yazdani Y contributed to validation; Alsbihawi TQ, and Mohammadi S contributed to formal analysis; Alsbihawi TQ, Ebrahimabad MZ, and Mohammadi S contributed to investigation; Alsbihawi TQ, Mohammadi S, and Yazdani Y contributed to resources; Alsbihawi TQ, Mohammadi S, and Yazdani Y contributed to data curation; Alsbihawi TQ, Ebrahimabad MZ, Seyedhosseini FS, Davoodi H, Abdolahi N, Mohammadi S, and Yazdani Y contributed to writing – original draft preparation; Alsbihawi TQ, Ebrahimabad MZ, Seyedhosseini FS, Davoodi H, Abdolahi N, Mohammadi S, and Yazdani Y contributed to writing – review and editing; Mohammadi S and Yazdani Y contributed to supervision; Mohammadi S and Yazdani Y contributed to project administration; Mohammadi S and Yazdani Y contributed to funding acquisition; All authors have read and approved the final version of the manuscript.
Supported by the Department of Research and Technology at Golestan University of Medical Sciences, No. 113017.
Institutional review board statement: The study obtained approval from the ethics committee at Golestan University of Medical Sciences (Code of Ethics: IR.GOUMS.REC.1401.261).
Informed consent statement: All participants provided informed consent prior to their involvement. Utmost confidentiality and privacy were ensured throughout the study, and precautionary measures were implemented to prevent any form of undue influence or coercion.
Conflict-of-interest statement: All the authors declare that there are no conflicts of interest to disclose.
Data sharing statement: The data supporting the findings of this study will be made accessible upon reasonable request by the corresponding author, Dr. Saeed Mohammadi (s.mohammadi@goums.ac.ir).
STROBE statement: The authors have read the STROBE Statement – checklist of items, and the manuscript was prepared and revised according to the STROBE Statement – checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Saeed Mohammadi, PhD, Assistant Professor, Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, R9Q4+242, Gorgan 49341-74515, Iran. s.mohammadi@goums.ac.ir
Received: July 14, 2023
Peer-review started: July 14, 2023
First decision: September 13, 2023
Revised: September 18, 2023
Accepted: October 23, 2023
Article in press: October 23, 2023
Published online: December 20, 2023
Abstract
BACKGROUND

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder impacting multiple organs, influenced by genetic factors, especially those related to the immune system. However, there is a need for new biomarkers in SLE. MicroRNA-125a (miR-125a) levels are decreased in T cells, B cells, and dendritic cells of SLE patients. MiR-125a plays a regulatory role in controlling the levels of tumor necrosis factor-alpha (TNF-α) and interleukin 12 (IL-12), which are crucial pro-inflammatory cytokines in SLE pathogenesis.

AIM

To assess the levels of miR-125a, IL-12, and TNF-α in SLE patients’ plasma, evaluating their diagnostic and prognostic value.

METHODS

The study included 100 healthy individuals, 50 newly diagnosed (ND), and 50 SLE patients undergoing treatment. The patients were monitored for a duration of 24 wk to observe and record instances of relapses. MiR-125a expression was measured using real-time reverse transcription polymerase chain reaction, while ELISA kits were used to assess IL-12 and TNF-α production.

RESULTS

The results showed significantly reduced miR-125a expression in SLE patients compared to healthy individuals, with the lowest levels in ND patients. TNF-α and IL-12 expression levels were significantly elevated in SLE patients, especially in the early stages of the disease. Receiver operating characteristic curve analyses, and Cox-Mantel Log-rank tests indicated miR-125a, TNF-α, and IL-12 as proper diagnostic biomarkers for SLE. A negative correlation was found between plasma miR-125a expression and IL-12/TNF-α levels in SLE patients.

CONCLUSION

Decreased miR-125a levels may be involved in the development of SLE, while elevated levels of IL-12 and TNF-α contribute to immune dysregulation. These findings offer new diagnostic and prognostic markers for SLE. Moreover, the negative correlation observed suggests an interaction between miR-125a, TNF-α, and IL-12. Further research is necessary to uncover the underlying mechanisms that govern these relationships.

Keywords: Systemic lupus erythematosus, microRNA-125a, Interleukin-12, Tumor necrosis factor alpha, Biomarker

Core Tip: The aim of this study was to investigate the levels of microRNA-125a (miR-125a), interleukin 12 (IL-12), and tumor necrosis factor-alpha (TNF-α) in the plasma of systemic lupus erythematosus (SLE) patients, and assess the diagnostic and prognostic value of these biomarkers in SLE. The study included healthy individuals, newly diagnosed SLE patients, and SLE patients undergoing treatment. The results revealed decreased levels of miR-125a in SLE patients, particularly in newly diagnosed cases. On the other hand, elevated levels of IL-12 and TNF-α were observed in SLE patients, especially in the early stages of the disease. The study also identified miR-125a, TNF-α, and IL-12 as potential diagnostic biomarkers for SLE. The negative correlation observed between miR-125a and IL-12/TNF-α suggests an interaction between these factors. These findings provide insights into new diagnostic and prognostic markers for SLE, highlighting the importance of immune dysregulation in the disease.