Skip to main content
Top
Published in: Pediatric Nephrology 12/2007

01-12-2007 | Original Article

Identification of a urinary proteomic signature for lupus nephritis in children

Authors: Michiko Suzuki, Gary F. Ross, Kristina Wiers, Shannen Nelson, Michael Bennett, Murray H. Passo, Prasad Devarajan, Hermine I. Brunner

Published in: Pediatric Nephrology | Issue 12/2007

Login to get access

Abstract

The quest for reliable biomarkers of systemic lupus erythematosus (SLE) nephritis is an area of intense contemporary research. In this study, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) technology was used for urinary proteomic profiling of patients with SLE nephritis. Clinical, laboratory, and kidney biopsy data from pediatric patients with SLE (n = 32) were analyzed. Children with juvenile idiopathic arthritis (n = 11) served as controls. SELDI-TOF-MS was performed using ProteinChips with different chromatographic surfaces. The resulting spectra were analyzed with Bio-Rad Biomarker Wizard software. A consistent urinary proteomic signature for SLE nephritis was found, comprising eight biomarker proteins with peaks at m/z of 2.7, 22, 23, 44, 56, 79, 100, and 133 kDa. The peak intensities of these biomarkers were significantly greater in patients with SLE nephritis compared with controls and SLE patients without nephritis. These biomarkers were strongly correlated with renal disease activity and moderately with renal damage. For the diagnosis of active nephritis, the area under the receiver operating characteristic curve was ≥0.90 for 22, 23, 44, 79, and 100 kDa biomarkers. Thus, SELDI-TOF-MS has identified a urine proteomic signature strongly associated with SLE renal involvement and active SLE nephritis.
Literature
1.
go back to reference Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725CrossRef Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725CrossRef
2.
go back to reference Ho A, Barr SG, Magder LS, Petri M (2001) A decrease in complement is associated with increased renal and hematologic activity in patients with systemic lupus erythematosus. Arthritis Rheum 44:2350–2357CrossRef Ho A, Barr SG, Magder LS, Petri M (2001) A decrease in complement is associated with increased renal and hematologic activity in patients with systemic lupus erythematosus. Arthritis Rheum 44:2350–2357CrossRef
3.
go back to reference Schiffenbauer J, Hahn B, Weisman MH, Simon LS (2004) Biomarkers, surrogate markers, and design of clinical trials of new therapies for systemic lupus erythematosus. Arthritis Rheum 50:2415–2422CrossRef Schiffenbauer J, Hahn B, Weisman MH, Simon LS (2004) Biomarkers, surrogate markers, and design of clinical trials of new therapies for systemic lupus erythematosus. Arthritis Rheum 50:2415–2422CrossRef
4.
go back to reference Cutillas P, Burlingame A, Unwin R (2004) Proteomic strategies and their application in studies of renal function. News Physiol Sci 19:114–119PubMed Cutillas P, Burlingame A, Unwin R (2004) Proteomic strategies and their application in studies of renal function. News Physiol Sci 19:114–119PubMed
5.
go back to reference Gunawardana CG, Diamandis EP (2007) High throughput proteomic strategies for identifying tumor-associated antigens. Cancer Lett 249:110–119CrossRef Gunawardana CG, Diamandis EP (2007) High throughput proteomic strategies for identifying tumor-associated antigens. Cancer Lett 249:110–119CrossRef
6.
go back to reference Hewitt SM, Dear J, Star RA (2004) Discovery of protein biomarkers for renal diseases. J Am Soc Nephrol 15:1677–1689CrossRef Hewitt SM, Dear J, Star RA (2004) Discovery of protein biomarkers for renal diseases. J Am Soc Nephrol 15:1677–1689CrossRef
7.
go back to reference Nguyen MT, Ross GF, Dent CL, Devarajan P (2005) Early prediction of acute renal injury using urinary proteomics. Am J Nephrol 25:318–326CrossRef Nguyen MT, Ross GF, Dent CL, Devarajan P (2005) Early prediction of acute renal injury using urinary proteomics. Am J Nephrol 25:318–326CrossRef
8.
go back to reference Schaub S, Wilkins J, Weiler T, Sangster K, Rush D, Nickerson P (2004) Urine protein profiling with surface-enhanced laser-desorption/ionization time-of-flight mass spectrometry. Kidney Int 65:323–332CrossRef Schaub S, Wilkins J, Weiler T, Sangster K, Rush D, Nickerson P (2004) Urine protein profiling with surface-enhanced laser-desorption/ionization time-of-flight mass spectrometry. Kidney Int 65:323–332CrossRef
9.
go back to reference Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, He X, Maldonado-Cocco J, Orozco-Alcala J, Prieur AM, Suarez-Almazor ME, Woo P (2004) International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 31:390–392PubMed Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, He X, Maldonado-Cocco J, Orozco-Alcala J, Prieur AM, Suarez-Almazor ME, Woo P (2004) International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 31:390–392PubMed
10.
go back to reference Gladman DD, Ibanez D, Urowitz MB (2002) Systemic lupus erythematosus disease activity index 2000. J Rheumatol 29:288–291PubMed Gladman DD, Ibanez D, Urowitz MB (2002) Systemic lupus erythematosus disease activity index 2000. J Rheumatol 29:288–291PubMed
11.
go back to reference Brunner HI, Feldman BM, Bombardier C, Silverman ED (1999) Sensitivity of the Systemic Lupus Erythematosus Disease Activity Index. British Isles Lupus Assessment Group Index, and Systemic Lupus Activity Measure in the evaluation of clinical change in childhood-onset systemic lupus erythematosus. Arthritis Rheum 42:1354–1360CrossRef Brunner HI, Feldman BM, Bombardier C, Silverman ED (1999) Sensitivity of the Systemic Lupus Erythematosus Disease Activity Index. British Isles Lupus Assessment Group Index, and Systemic Lupus Activity Measure in the evaluation of clinical change in childhood-onset systemic lupus erythematosus. Arthritis Rheum 42:1354–1360CrossRef
12.
go back to reference Hay EM, Bacon PA, Gordon C, Isenberg DA, Maddison P, Snaith ML, Symmons DP, Viner N, Zoma A (1993) The BILAG index: a reliable and valid instrument for measuring clinical disease activity in systemic lupus erythematosus. Q J Med 86:447–458PubMed Hay EM, Bacon PA, Gordon C, Isenberg DA, Maddison P, Snaith ML, Symmons DP, Viner N, Zoma A (1993) The BILAG index: a reliable and valid instrument for measuring clinical disease activity in systemic lupus erythematosus. Q J Med 86:447–458PubMed
13.
go back to reference Gladman DD, Goldsmith CH, Urowitz MB, Bacon P, Fortin P, Ginzler E, Gordon C, Hanly JG, Isenberg DA, Petri M, Nived O, Snaith M, Sturfelt G (2000) The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index for Systemic Lupus Erythematosus International Comparison. J Rheumatol 27:373–376PubMed Gladman DD, Goldsmith CH, Urowitz MB, Bacon P, Fortin P, Ginzler E, Gordon C, Hanly JG, Isenberg DA, Petri M, Nived O, Snaith M, Sturfelt G (2000) The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index for Systemic Lupus Erythematosus International Comparison. J Rheumatol 27:373–376PubMed
14.
go back to reference Weening JJ, D’Agati VD, Schwartz MM (2004) The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int 65:521–530CrossRef Weening JJ, D’Agati VD, Schwartz MM (2004) The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int 65:521–530CrossRef
15.
go back to reference Churg J, Bernstein J, Glassock RJ (1995) Renal disease: classification and atlas of glomerular diseases, 2nd edn. Igaku-Shoin, New York Churg J, Bernstein J, Glassock RJ (1995) Renal disease: classification and atlas of glomerular diseases, 2nd edn. Igaku-Shoin, New York
16.
go back to reference Brunner HI, Mueller M, Rutherford C, Passo MH, Witte D, Grom A, Mishra J, Devarajan P (2006) Urinary neutrophil gelatinase-associated lipocalin as a biomarker of nephritis in childhood-onset systemic lupus erythematosus. Arthritis Rheum 54:2577–2584CrossRef Brunner HI, Mueller M, Rutherford C, Passo MH, Witte D, Grom A, Mishra J, Devarajan P (2006) Urinary neutrophil gelatinase-associated lipocalin as a biomarker of nephritis in childhood-onset systemic lupus erythematosus. Arthritis Rheum 54:2577–2584CrossRef
17.
go back to reference Hanley JA (1989) Receiver operating characteristic (ROC) methodology: the state of the art. Crit Rev Diagn Imaging 29:307–335PubMed Hanley JA (1989) Receiver operating characteristic (ROC) methodology: the state of the art. Crit Rev Diagn Imaging 29:307–335PubMed
18.
go back to reference Oates JC, Varghese S, Bland AM, Taylor TP, Self SE, Stanislaus R, Almeida JS, Arthur JM (2005) Prediction of urinary protein markers in lupus nephritis. Kidney Int 68:2588–2592CrossRef Oates JC, Varghese S, Bland AM, Taylor TP, Self SE, Stanislaus R, Almeida JS, Arthur JM (2005) Prediction of urinary protein markers in lupus nephritis. Kidney Int 68:2588–2592CrossRef
19.
go back to reference Varghese SA, Powell TB, Budisavljevic MN, Oates JC, Raymond JR, Almeida JS, Arthur JM (2007) Urine biomarkers predict the cause of glomerular disease. J Am Soc Nephrol 18:913–922CrossRef Varghese SA, Powell TB, Budisavljevic MN, Oates JC, Raymond JR, Almeida JS, Arthur JM (2007) Urine biomarkers predict the cause of glomerular disease. J Am Soc Nephrol 18:913–922CrossRef
20.
go back to reference Gudehithlu KP, Pegoraro AA, Dunea G, Arruda JA, Singh AK (2004) Degradation of albumin by the renal proximal tubule cells and the subsequent fate of its fragments. Kidney Int 65:2113–2122CrossRef Gudehithlu KP, Pegoraro AA, Dunea G, Arruda JA, Singh AK (2004) Degradation of albumin by the renal proximal tubule cells and the subsequent fate of its fragments. Kidney Int 65:2113–2122CrossRef
21.
go back to reference Strong KJ, Osicka TM, Comper WD (2005) Urinary-peptide excretion by patients with and volunteers without diabetes. J Lab Clin Med 145:239–246CrossRef Strong KJ, Osicka TM, Comper WD (2005) Urinary-peptide excretion by patients with and volunteers without diabetes. J Lab Clin Med 145:239–246CrossRef
22.
go back to reference Mosley K, Tam FW, Edwards RJ, Crozier J, Pusey CD, Lightstone L (2006) Urinary proteomic profiles distinguish between active and inactive lupus nephritis. Rheumatology (Oxford) 45:1497–1504CrossRef Mosley K, Tam FW, Edwards RJ, Crozier J, Pusey CD, Lightstone L (2006) Urinary proteomic profiles distinguish between active and inactive lupus nephritis. Rheumatology (Oxford) 45:1497–1504CrossRef
23.
go back to reference Li Y, Tucci M, Narain S, Barbes EV, Sobel ES, Segal MS, Richards HB (2006) Urinary biomarkers in lupus nephritis. Autoimmun Rev 5:383–388CrossRef Li Y, Tucci M, Narain S, Barbes EV, Sobel ES, Segal MS, Richards HB (2006) Urinary biomarkers in lupus nephritis. Autoimmun Rev 5:383–388CrossRef
Metadata
Title
Identification of a urinary proteomic signature for lupus nephritis in children
Authors
Michiko Suzuki
Gary F. Ross
Kristina Wiers
Shannen Nelson
Michael Bennett
Murray H. Passo
Prasad Devarajan
Hermine I. Brunner
Publication date
01-12-2007
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 12/2007
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-007-0608-x

Other articles of this Issue 12/2007

Pediatric Nephrology 12/2007 Go to the issue

Abstracts

Abstracts