ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 385

Urinary Cell-Free Microrna’s As Biomarkers of Lupus Nephritis in Children

Khalid Abulaban1, Ndate Fall2, Jun Ying3, Kasha Wiley4, Ravi Nunna3, Prasad Devarajan5, Alexei A. Grom4, Michael Bennett6, Stacy P. Ardoin7 and Hermine I. Brunner8, 1Pediatric Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 2Division of Rheumatology, Cincinnati Children's Hospital, Cincinnati, OH, 3University of Cincinnati, Cincinnati, OH, 4Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 5Dept of Nephrology, Cincinnati Children`s Hospital Medical Center, Cincinnati, OH, 6Division of Nephrology, Cincinnati Children`s Hospital Medical Center, Cincinnati, OH, 7Pediatric & Adult Rheumatology, Ohio State University, Columbus, OH, 8Pediatric Rheumatology Collaborative Study Group, Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: ,

Session Information

Date: Sunday, November 8, 2015

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

Disclosure: K. Abulaban, None; N. Fall, None; J. Ying, None; K. Wiley, None; R. Nunna, None; P. Devarajan, None; A. A. Grom, None; M. Bennett, None; S. P. Ardoin, None; H. I. Brunner, None.

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 .

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