Session Information
Date: Sunday, November 8, 2015
Session Title: Pediatric Rheumatology – Clinical and Therapeutic Aspects Poster I: Lupus, Scleroderma, JDMS
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose:
MicroRNAs (miRNAs) are single-stranded RNAs involved in the regulation of host genome expression at the post-transcriptional level. 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:
In this prospective longitudinal cohort study, 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 SLE, and 10 controls (five juvenile idiopathic arthritis and five fibromyalgia patients). The concentrations of the LN-Panel biomarkers were also assayed. Traditional LN-measures (complement levels of C3 and C4, anti-dsDNA antibodies, protein to creatinine ratio) and the renal and extra-renal disease activity were measured using renal and extra-renal domain scores of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), respectively.
Results:
SUP levels of miR-125a, miR-150, and miR-155 were at least weak to strongly associated with most of the LN-Panel biomarkers (Pearson correlation coefficients; 0.3 < r < 0.9; p<0.05), but generally no more than weakly with the renal domain of the SLEDAI or traditional LN-measures (r-<0.5)(table). In the PEL, miRNA levels did not correlate with any of the LN-measure (LN-Panel, traditional LN-measures, renal-SLEDAI).
Conclusion:
Levels of cell-free miR-125a, miR-150, and miR-155 in the urine supernatant but not the sediment are differentially excreted with active LN and may complement, but are unlikely superior to the LN-Panel for estimating concurrent LN activity.
|
Table:Associations of MiRNA levels in the urine supernatant vs. traditional measures |
||||||||||
|
Variables ** |
miR125a |
miR127 |
miR146a |
miR150 |
miR155 |
|||||
|
LN-Panel |
|
|
|
|
|
|||||
|
Transferrin |
0.44 |
-0.24 |
– |
0.65 |
0.54 |
|||||
|
BTP |
0.73 |
-0.24 |
-0.37 |
0.68 |
0.35 |
|||||
|
NGAL |
0.48 |
– |
-0.27 |
0.39 |
– |
|||||
|
MCP-1 |
0.44 |
0.34 |
– |
0.45 |
0.68 |
|||||
|
WBC (k/mcL) |
0.23 |
– |
– |
0.40 |
– |
|||||
|
Hemoglobin (mg/dL) |
– |
– |
– |
– |
– |
|||||
|
Platelets count (k/mcL) |
-0.39 |
-0.24 |
– |
– |
– |
|||||
|
ESR (mm/hr) |
– |
0.24 |
– |
– |
– |
|||||
|
Anti-dsDNA titer |
– |
-0.33 |
-0.30 |
– |
-0.29 |
|||||
|
C3 level (mg/dL) |
-0.32 |
– |
0.24 |
— |
-0.36 |
|||||
|
C4 level (mg/dL) |
– |
– |
– |
– |
-0.29 |
|||||
|
Total SLEDAI* |
0.31 |
– |
-0.28 |
– |
– |
|||||
|
Renal – SLEDAI¹ |
– |
– |
-0.32 |
– |
– |
|||||
|
Extrarenal SLEDAI² |
0.27 |
– |
– |
– |
– |
|||||
**Values are Pearson correlation coefficients of log-transformed urine concentrations the miRNAs listed with
miR, micro RNA ; BTP, beta trace protein ; NGAL, neutrophil gelatinase associated lipocalin ; MCP, monocyte chemotactic protein 1; WBC, white blood count ; DSDNA, anti-double stranded DNA titer ;
* SLEDAI, Systemic Lupus Erythematosus Disease Activity Index, range 0 – 105; 0 inactive LN
¹Renal-SLEDAI, renal domain of the Systemic Lupus Erythematosus Disease Activity Index.
²Extrarenal SLEDAI, Sum of the Systemic Lupus Erythematosus Disease Activity Index except the renal domain score
To cite this abstract in AMA style:
Abulaban K, Fall N, Ying J, Wiley K, Nunna R, Devarajan P, Grom AA, Bennett M, Ardoin SP, Brunner HI. Urinary Cell-Free Microrna’s As Biomarkers of Lupus Nephritis in Children [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/urinary-cell-free-micrornas-as-biomarkers-of-lupus-nephritis-in-children/. Accessed July 23, 2019.« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/urinary-cell-free-micrornas-as-biomarkers-of-lupus-nephritis-in-children/