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Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
Published on: June 8, 2022
Relationship of cell-free urine MicroRNA with lupus nephritis in children
Khalid M Abulaban1,2, Ndate Fall3, Ravi Nunna4
1Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. khalidabulaban@hotmail.com.
Background:
MicroRNAs (miRNAs) are involved in the post-transcriptional regulation of genes. The objective of this study was to investigate whether select urinary cell-free microRNA's may serve as biomarkers in children with active lupus nephritis (LN) and to assess their relationship to the recently identified combinatorial urine biomarkers, a.k.a. the LN-Panel (neutrophil gelatinase associated lipocalin, monocyte chemotactic protein 1, transferrin, and beta-trace protein).
Methods:
miRNAs (125a, 127, 146a, 150 and 155) were measured using real-time polymerase chain reaction in the urine pellet (PEL) and supernatant (SUP) in 14 patients with active LN, 10 patients with active extra-renal lupus, and 10 controls. The concentrations of the LN-Panel biomarkers (neutrophil gelatinase associated lipocalin, monocyte chemotactic protein-1, transferrin, beta-trace protein) was assayed. Traditional laboratory and clinical measures of LN and lupus (complements, protein to creatinine ratio; Systemic Lupus Erythematosus Disease Activity Index) were also measured.
Results:
All tested miRNAs in the SUP, but not the PEL, were associated with the LN-Panel biomarkers (0.3 < |r Pearson| < 0.73; p < 0.05), miRNA125a, miRNA127,miRNA146a also with C3 and dsDNA antibody levels (|r Pearson| > 0.24; p < 0.05), and miRNA146a with the renal domain of the SLEDAI (|r Pearson| = 0.32; p < 0.05). Mean miRNA levels of patients with active LN did not statistically (P > 0.05) differ from those of SLE patients without LN or controls.
Conclusion:
Levels of cell-free miR-125a, miR-150, and miR-155 in the urine supernatant are associated with the expression of LN-Panel biomarkers and some LN measures. These miRNA's may complement, but are unlikely superior to the LN-Panel for estimating concurrent LN activity.
Insights
Urinary cell-free microRNAs (miRNAs) correlate with lupus nephritis biomarkers in children. While these miRNAs may supplement existing tests, they are unlikely to replace the established LN-Panel for assessing disease activity.
Area of Science:
- Pediatric Nephrology
- Molecular Biology
- Immunology
Background:
- MicroRNAs (miRNAs) regulate gene expression post-transcriptionally.
- Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE).
- Urinary biomarkers are crucial for diagnosing and monitoring LN activity.
Purpose of the Study:
- To investigate urinary cell-free microRNAs as potential biomarkers in pediatric lupus nephritis.
- To assess the relationship between specific urinary miRNAs and the established LN-Panel biomarkers.
- To evaluate the utility of miRNAs in reflecting LN disease activity.
Main Methods:
- Measurement of selected miRNAs (125a, 127, 146a, 150, 155) in urine supernatant and pellet using real-time PCR.
- Assay of LN-Panel biomarkers (NGAL, MCP-1, transferrin, beta-trace protein).
- Assessment of traditional LN and SLE measures (complement levels, proteinuria, SLEDAI).
Main Results:
- Urinary supernatant miRNAs (but not pellet) correlated with LN-Panel biomarkers.
- Specific miRNAs (125a, 127, 146a) showed associations with complement C3 and anti-dsDNA antibody levels.
- miRNA146a correlated with the renal domain of the SLEDAI, indicating a link to disease activity.
Conclusions:
- Cell-free miRNAs in urine supernatant are associated with LN-Panel biomarkers and certain LN activity measures.
- These miRNAs may serve as complementary biomarkers for assessing concurrent LN activity.
- The studied miRNAs are unlikely to be superior to the LN-Panel for estimating LN activity.
