Urinary proteomic profiles distinguish between active and inactive lupus nephritis.
OBJECTIVE
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.
Mosley
K
K
Renal Section, Division of Medicine, Imperial College London, Hammersmith Campus, London, UK. k.mosley@imperial.ac.uk
Tam
F W K
FW
Edwards
R J
RJ
Crozier
J
J
Pusey
C D
CD
Lightstone
L
L
D000328:Adult; D015415:Biomarkers / Q000652:urine; D003404:Creatinine / Q000097:blood / Q000652:urine; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000652:urine; D008181:Lupus Nephritis / Q000150:complications / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D040081:Protein Array Analysis / Q000379:methods; D011507:Proteinuria / Q000209:etiology / Q000652:urine*; D040901:Proteomics; D012008:Recurrence; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D015415:Biomarkers; D003404:Creatinine