Rheumatology Advance Access originally published online on October 17, 2006
Rheumatology 2006 45(12):1497-1504; doi:10.1093/rheumatology/kel351
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© 2006 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Urinary proteomic profiles distinguish between active and inactive lupus nephritis
Renal Section and 1Experimental Medicine and Toxicology, Division of Medicine, Imperial College London, Hammersmith Campus, London W12 0NN, UK.
Correspondence to: K. Mosley, Renal Section, Division of Medicine, Imperial College London, Hammersmith Campus, London W12 0NN, UK. E-mail: k.mosley{at}imperial.ac.uk.
Objectives. Key aims of the treatment of lupus nephritis (LN) are to induce and maintain remission with minimal side effects. However, assessing ongoing renal inflammatory activity is poorly served by current diagnostic tests apart from renal biopsy, but frequent biopsies cannot be justified. Our long-term aim is to identify novel biomarkers from urinary protein profiles to improve diagnosis and monitoring of activity and response to therapy in LN.
Methods. We used surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) to identify biomarkers able to discriminate between urine samples from patients with inactive (n= 49) and active (n= 26) LN. Discriminant function analysis was used to define the minimum number of proteins whose levels best distinguished between the two patient groups. Serial urines of six biopsied patients were studied prospectively, and multiple regression (MR) scores calculated.
Results. Proteins with masses of 3340 and 3980 distinguished active from inactive LN with 92% sensitivity and specificity of 92% each. The prospective study of the biopsied patients demonstrated that MR scores could predict both relapse and remission earlier than traditional clinical markers.
Conclusions. SELDI-TOF MS identified potential biomarker profiles strongly associated with activity in LN. Identification of these proteins will allow us to devise specific assays to routinely monitor disease progression, and alter immunosuppressive drug regimens accordingly. These proteins may also play a critical role in the pathogenesis of glomerulonephritis, and could therefore provide targets for therapeutic intervention.
KEY WORDS: Lupus nephritis, Biomarkers, SELDI-TOF MS
This work presented in part at the 38th Annual meeting of the American Society of Nephrology, Philadelphia, 2005. (Lightstone L, Mosley K, Edwards RJ, Crozier J, Pusey CD and Tam FWK. Urinary proteomic profiles are able to discriminate between active and inactive lupus nephritis. J Am Soc Nephrol 2005;16:8A.)
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