Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.


Urinary Biomarkers May Differentiate Between Children with ISN/RPS Class IV Versus Class V of Lupus Nephritis (LN)

Das1,  Lena, Suzuki1,  Michiko, Bennett1,  Michael, Haines2,  Kathleen A., Klein-Gitelman3,  Marisa, Olson4,  Judyann C., Onel5,  Karen

Cincinnati Children's Hospital Medical Center, Cincinnati, OH,
University of Cincinnati, Cincinnati, OH
Hackensack Univ Med Ctr, Hackensack, NJ,
Children's Memorial Hospital, Chicago, IL,
Med Coll of Wisconsin, Milwaukee, WI,
Univ of Chicago, Chicago, IL,
Oklahoma University Health Science Ctr, Oklahoma City, OK,
Hospital for Sick Children and University of Toronto. Toronto, ON,
University Hospitals/Case Medical Center/Rainbow Babies and Children's Hospital. Cleveland, OH,
BC Childrens Hospital, Vancouver, BC,

Purpose:

Biopsy-proven LN occurs in up to 75% of all children with SLE. ISN/RPS classes of LN differ in major histological features, clinical manifestations and prognosis. Our aim was to identify urinary biomarkers that can differentiate between ISN/RPS class IV and class V in children with LN.

Method:

In this ongoing study, urine samples from children with LN ISN/RPS class IV (n=6) and pure class V (n=7) collected within 60 days of a kidney biopsy and those of controls with focal segmental glomerulosclerosis (n=4) were tested. Two proteomic methods were employed that reliably measure large and mid-molecular weight proteins, i.e. 2-dimensional gel electrophoresis (2-DGE) and surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS), respectively. Candidate biomarker proteins were selected if levels differed significantly when comparing class IV vs. V, class IV vs. controls, or class V vs. controls. The identity of relevant protein spots seen on 2-DGE was obtained by MALDI-TOF-MS/MS.

Results:

Using 2-DGE and MALDI-TOF-MS/MS, we found human serum albumin fragments (25kDa) and a1-B glycoprotein (60kDa) significantly over-expressed in class IV vs. class V LN. For SELDI-TOF-MS/MS four different chromatographic surfaces were tested; spectra were analyzed with ProteinChip Data Manager 3.07. The resulting urinary signature of mid-molecular weight proteins that differed between groups of samples based on robust and reproducible peaks is shown in the Table, with areas under the receiver operating characteristic curves > 0.7 (all p < 0.05).

SELDI ProteinChip type of chromatographic surface#Class IV vs. class V*Controls vs. class IV**Controls vs. class V**
Cation exchange78073273 
  3323 
Normal phase3266393623119
 32784270 
  4478 
  7787 
  23119 
    
    
Hydrophobic binding381638764475
 387667964631
 4247161347634
 58352583511830
 90752810111958
 9452 13080
 16673 47905
Metal affinity4349150967035
 46391529815096
 47026641115298
 8846138089 
  148232 
#Values are MS peaks at m/z of Da;
*Peaks (Da) with fold change >2;
**Peaks (Da) with fold change > 10

Conclusion:

We have identified two proteins and a urinary biomarker signature that appear to be significantly different between LN ISN/RPS class IV and class V. Further studies in larger patient groups, including adults with SLE, are needed to confirm our findings and to assess the diagnostic accuracy of these candidate biomarkers.

To cite this abstract, please use the following information:
Das, Lena, Suzuki, Michiko, Bennett, Michael, Haines, Kathleen A., Klein-Gitelman, Marisa, Olson, Judyann C., et al; Urinary Biomarkers May Differentiate Between Children with ISN/RPS Class IV Versus Class V of Lupus Nephritis (LN) [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1527
DOI: 10.1002/art.26601

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