Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Urinary Biomarkers To Distinguish Class IV vs Class V Lupus Nephritis.

Brunner1,  Hermine, Bennett2,  Michael, Romick-Rosendale5,  Lindsey, Suzuki3,  Michiko, Nelson2,  Shannen L., Pendl3,  Joshua, Kiani4,  Adnan

Cincinnati Child Hosp Med Ctr, Cincinnati, OH
Cincinnati Children's Med Ctr, Cincinnati, OH
Cincinnati Children's Med Ctr
John Hopkins Med Ctr
Miami University, Oxford
University of Cincinnati
WPAFB, Dayton

Background:

Up to 80% of children with systemic lupus erythematosus have lupus nephritis (LN). The ISN/RPS Morphologic Classification of LN reports on histological features that differentiate between various forms of LN, such as Diffuse Proliferative Class IV and Membranous Class V lesions. Kidney biopsies are the choice for diagnosis of LN, but are impractical to accurately assess the course of LN in clinical practice.

Objective:

Discover non-invasive urinary biomarkers that can discriminate LN subtypes using proteomics, peptidomics and metabonomics.

Methods:

We used 2-dimensional gel electrophoresis (2-DGE), NMR-based metabonomics, surface-enhanced laser desorption/ionization time of flight MS (SELDI), and iTRAQ liquid chromatography tandem mass spectrometry (LC MS/MS2) to investigate novel biomarkers that could distinguish Class IV vs. Class V LN. Urine samples from children with Class IV LN (n=6) and (pure) Class V LN (n=7) collected within 60 days of a kidney biopsy and those of controls with focal segmental glomerulosclerosis (n=4) were tested. Samples were normalized for total protein (2-DGE and LC-MS/MS2) or urine creatinine (NMR and SELDI).

Results:

Using 2-DGE and MALDI-TOF-MS/MS, we found serum albumin fragments (25kDa) and alpha1-B glycoprotein (A1BG, 60kDa) significantly over-expressed in class IV vs. class V LN. Using SELDI, we identified Alpha-1 Antitrypsin (A1AT). This protein was significantly (p < 0.01; AUC 0.90) over-expressed in Class V vs Class IV LN and FSGS controls. Principal component analysis of NMR metabonomics spectra suggests decreased levels of citrate and increased levels of taurine in Class V when compared to Class IV patients, while iTRAQ -LC-MS/MS2 uncovered the most differences between the groups. Among proteins upregulated in Class V LN were apolipoprotein D, lipocalin-like prostaglandin D synthetase, inter-alpha-trypsin inhibitor heavy chain 4, Caspase 10, uromodulin and CD14. Those most upregulated in Class IV LN were vitamin D binding protein, ceruloplasmin, hemopexin, A1BG and orosomucoid. A1AT has been linked to SLE flares and hemopexin is associated with glomerular disease.

Conclusions:

The discovery of non-invasive biomarkers that can distinguish LN subtypes would greatly aid in diagnosing and monitoring treatment in LN.

To cite this abstract, please use the following information:
Brunner, Hermine, Bennett, Michael, Romick-Rosendale, Lindsey, Suzuki, Michiko, Nelson, Shannen L., Pendl, Joshua, et al; Urinary Biomarkers To Distinguish Class IV vs Class V Lupus Nephritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :268
DOI: 10.1002/art.28037

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