Skip to main content
SpringerLink
Log in

Identification of a urinary proteomic signature for lupus nephritis in children

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725

    Article  CAS  Google Scholar 

  2. 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 44:2350–2357

    Article  CAS  Google Scholar 

  3. 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 50:2415–2422

    Article  Google Scholar 

  4. Cutillas P, Burlingame A, Unwin R (2004) Proteomic strategies and their application in studies of renal function. News Physiol Sci 19:114–119

    CAS  PubMed  Google Scholar 

  5. Gunawardana CG, Diamandis EP (2007) High throughput proteomic strategies for identifying tumor-associated antigens. Cancer Lett 249:110–119

    Article  CAS  Google Scholar 

  6. Hewitt SM, Dear J, Star RA (2004) Discovery of protein biomarkers for renal diseases. J Am Soc Nephrol 15:1677–1689

    Article  Google Scholar 

  7. Nguyen MT, Ross GF, Dent CL, Devarajan P (2005) Early prediction of acute renal injury using urinary proteomics. Am J Nephrol 25:318–326

    Article  CAS  Google Scholar 

  8. 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 65:323–332

    Article  CAS  Google Scholar 

  9. 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 31:390–392

    PubMed  Google Scholar 

  10. Gladman DD, Ibanez D, Urowitz MB (2002) Systemic lupus erythematosus disease activity index 2000. J Rheumatol 29:288–291

    PubMed  Google Scholar 

  11. 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 42:1354–1360

    Article  CAS  Google Scholar 

  12. 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 86:447–458

    CAS  PubMed  Google Scholar 

  13. 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 27:373–376

    CAS  PubMed  Google Scholar 

  14. Weening JJ, D’Agati VD, Schwartz MM (2004) The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int 65:521–530

    Article  Google Scholar 

  15. Churg J, Bernstein J, Glassock RJ (1995) Renal disease: classification and atlas of glomerular diseases, 2nd edn. Igaku-Shoin, New York

    Google Scholar 

  16. 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 54:2577–2584

    Article  CAS  Google Scholar 

  17. Hanley JA (1989) Receiver operating characteristic (ROC) methodology: the state of the art. Crit Rev Diagn Imaging 29:307–335

    CAS  PubMed  Google Scholar 

  18. 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 68:2588–2592

    Article  CAS  Google Scholar 

  19. 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 18:913–922

    Article  CAS  Google Scholar 

  20. 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 65:2113–2122

    Article  CAS  Google Scholar 

  21. Strong KJ, Osicka TM, Comper WD (2005) Urinary-peptide excretion by patients with and volunteers without diabetes. J Lab Clin Med 145:239–246

    Article  CAS  Google Scholar 

  22. 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) 45:1497–1504

    Article  CAS  Google Scholar 

  23. Li Y, Tucci M, Narain S, Barbes EV, Sobel ES, Segal MS, Richards HB (2006) Urinary biomarkers in lupus nephritis. Autoimmun Rev 5:383–388

    Article  CAS  Google Scholar 

Download references

Acknowledgement

This study is supported by a clinical research grant NIAMS P60 AR47784. Dr. Brunner is supported by a grant from the Alliance for Lupus Research and the CCHMC Translational Research Initiative. Dr. Devarajan is supported by grants from the NIH/NIDDK (RO1-DK53289, P50-DK52612, R21-DK070163). Dr. Wiers is supported by T32 AR007594 and the NIH Loan Repayment Program. We are indebted to our clinical coordinators Jamie Meyer-Eaton and Cynthia Rutherford for their assistance, Lukasz Itert for the data management, the NIAMS Tissue Repository (director Susan Thompson; AR047363) for the sample management, Alison Kissling for her technological support with the manuscript preparation, and to our patients and families for their participation.

Author information

Authors and Affiliations

  1. Division of Nephrology and Hypertension, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA

    Michiko Suzuki, Michael Bennett & Prasad Devarajan

  2. Biorad Bioscience Inc., Hercules, CA, USA

    Gary F. Ross

  3. William Rowe Division of Rheumatology, Cincinnati Children’s Hospital Medical Center, E 4010, 3333 Burnet Avenue, Cincinnati, OH, 45229-3039, USA

    Kristina Wiers, Shannen Nelson, Murray H. Passo & Hermine I. Brunner

Authors
  1. Michiko Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gary F. Ross
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kristina Wiers
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shannen Nelson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michael Bennett
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Murray H. Passo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Prasad Devarajan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hermine I. Brunner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hermine I. Brunner.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Suzuki, M., Ross, G.F., Wiers, K. et al. Identification of a urinary proteomic signature for lupus nephritis in children. Pediatr Nephrol 22, 2047–2057 (2007). https://doi.org/10.1007/s00467-007-0608-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-007-0608-x

Keywords

Search

Navigation