Urine Biomarkers Distinguish Between Proliferative and Membranous Lupus Nephritis in Childhood Onset Systemic Lupus Erythematosus

Rina Mina¹, Michael Bennett², Lining Qi³, Shannen Nelson⁴, Jessica Hummel⁵, Pavel Shiyanov³, John Schlager³, Prasad Devarajan² and Hermine Brunner⁶, ¹Rheumatology, Cincinnati Children's Hospital Medical Center/University of Cincinnati, Cincinnati, OH, ²Nephrology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, ³US Air Force Research Lab, Wright-Patterson Air Force Base, OH, ⁴Rheumatology, Cincinnati Children's Hospital, Cincinnati, OH, ⁵Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, ⁶Cincinnati Children's Hospital, Cincinnati, OH

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: Biomarkers, lupus nephritis and pediatrics

Session Information

Title: Pediatric Rheumatology: Clinical and Therapeutic Disease III: Childhood Systemic Lupus Erythematosus and Other Vasculidities

Session Type: Abstract Submissions (ACR)

Background/Purpose:

The ISN/RPS Morphologic Classification of Lupus Nephritis (LN) reports on histological features that differentiate among various forms of LN, most notably between proliferative and membranous classes which have different renal outcomes. There is a lack of non-invasive biomarkers that can discriminate between LN subtypes which are important so that appropriate therapies can be planned. We aim to investigate candidate urine biomarkers that will distinguish between proliferative and membranous LN in childhood onset systemic lupus erythematosus (cSLE).

Methods:

Using liquid chromatography tandem mass spectrometry proteomics, we isolated Vitamin-D Binding Protein (VDBP) and Prostaglandin D synthase (PGDS) from urine collected from 53 patients with LN. Levels of VDBP were measured using a commercially available ELISA assay and these were standardized to urine creatinine (UCr). Differences in the levels of VDBP between proliferative and membranous LN were analyzed using Mann-Whitney rank sum analysis. For PGDS, we performed spectral counting through ProteoIQ and validated the results with western blot.

Results:

There were 27 renal biopsies classified as proliferative LN and 26 were classified as membranous LN. Median levels in ng/ml (range) of urinary VDBP levels were significantly higher in proliferative LN compared to membranous LN [90.9 (IQR 28.9 – 948.4) versus 33.5 (IQR 21.3 – 124.1), p-value=0.046]. The results remained significant when VDBP levels were corrected for UCr [median in ng/mg (range) = 22.2 (29.0 – 1822.9) versus 44.1 (14.8 – 139.5), p-value=0.045]. PGDS was overexpressed in the urine of patients with membranous LN compared to proliferative LN with an average spectral count of 13 versus 4, respectively, and a ratio of 3.25 (p-value < 0.05). This difference was confirmed by western blot.

Conclusion:

We isolated two candidate urine biomarkers, Vitamin-D Binding Protein and Prostaglandin D synthase, and thereafter validated our proteomic finding that these can distinguish between proliferative LN and membranous LN. The discovery of these non-invasive biomarkers and its application in a clinically usable platform could lead to a substantial impact on management strategies for LN in cSLE.

Disclosure:

R. Mina,
None;

M. Bennett,
None;

L. Qi,
None;

S. Nelson,
None;

J. Hummel,
None;

P. Shiyanov,
None;

J. Schlager,
None;

P. Devarajan,
None;

H. Brunner,
None.

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