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Circulatory microRNAs and proinflammatory cytokines as predictors of lupus nephritis

Dalia Saad ElFeky¹, Noha Mohamed Omar¹, Olfat Gamil Shaker²

¹Department of Medical Microbiology and Immunology, Faculty of Medicine, Cairo University, Cairo, Egypt.

Frontiers in Immunology

|October 28, 2024

Abstract

Introduction:

Lupus nephritis (LN) is one of the most prevalent severe organ manifestations of systemic lupus erythematosus (SLE), impacting 70% of SLE patients. MicroRNAs (miRNAs), are small non-coding RNA molecules which influence the expression of approximately one-third of human genes after the process of transcription. Dysregulation of miRNAs was documented in numerous disorders, including SLE and LN. Cytokines are the orchestrators of the immune response in autoimmune diseases. Our study aims to explore the variation in the levels of circulating miRNAs and proinflammatory cytokines as potential diagnostic biomarkers among LN and SLE patients without LN in comparison to controls.

Methods:

The study involved 20 LN patients, 20 SLE patients without LN, and 10 healthy controls. Serum levels of IL-12 and IL-21 in addition to miR-124, miR-146a, miR-199a, and miR-21 were assessed using the enzyme-linked immunosorbent assay (ELISA) for cytokines and quantitative real-time PCR for miRNAs.

Results:

A significant downregulation in miR-124 (p<0.001) and a significant overexpression of miR-146a (p=0.005) were found in SLE patients without LN in comparison to controls. In comparison to SLE patients without LN and the control group, miR-199a, miR-21, and miR-146a were significantly upregulated in LN patients (p=<0.001) with high diagnostic values of these miRNAs in discriminating LN from SLE patients without LN according to Receiver operating curve (ROC) analysis. Logistic regression analysis revealed that only miR-199a is an independent predictor of LN (OR 1.69; 95% CI: 1.1-2.6). The expression of miR-124 was reduced in LN patients in comparison to the control but increased in LN patients in comparison to SLE patients without LN. However, there was no statistically significant difference in either scenario. In comparison to both SLE patients without LN and controls, LN patients exhibited the highest serum levels of IL-12 and IL-21, with no statistically significant difference. Regression analysis revealed that only miR-146a was associated with creatinine levels and SLEDAI score (p= 0.009 and 0.03, respectively), while miR-124 was associated with hemoglobin level (p=0.03).

Conclusion:

MiR-199a is an independent predictor for LN and might be used as a diagnostic biomarker for this disease. MiR-146a might play an important role in LN pathophysiology.

Insights

MicroRNA-199a is a potential biomarker for lupus nephritis (LN), an autoimmune kidney disease. This study found miR-199a levels could help diagnose LN in systemic lupus erythematosus (SLE) patients.

Area of Science:

Immunology
Genetics
Nephrology

Background:

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE), affecting a majority of patients.
MicroRNAs (miRNAs) are key regulators of gene expression, and their dysregulation is implicated in autoimmune diseases like SLE and LN.
Cytokines orchestrate immune responses, making them crucial in autoimmune pathogenesis.

Purpose of the Study:

To investigate circulating miRNA and cytokine profiles as potential diagnostic biomarkers in LN patients.
To differentiate LN patients from SLE patients without LN and healthy controls based on biomarker levels.

Main Methods:

Serum samples from 20 LN patients, 20 SLE patients without LN, and 10 healthy controls were analyzed.
Quantitative real-time PCR was used to measure levels of miR-124, miR-146a, miR-199a, and miR-21.
Enzyme-linked immunosorbent assay (ELISA) was employed to quantify serum levels of IL-12 and IL-21.

Main Results:

miR-199a, miR-21, and miR-146a were significantly upregulated in LN patients compared to controls and SLE patients without LN.
Receiver operating curve (ROC) analysis indicated high diagnostic value for these miRNAs in distinguishing LN.
Logistic regression identified miR-199a as an independent predictor of LN (OR 1.69).
miR-146a levels correlated with creatinine and SLEDAI score, while miR-124 correlated with hemoglobin.

Conclusions:

miR-199a shows promise as an independent diagnostic biomarker for lupus nephritis.
miR-146a may play a significant role in the pathophysiology of lupus nephritis.

Read full analysis

Keywords:

IL-12 IL-21 LN SLE miR-124 miR-146a miR-199a miR-21

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