Initial validation of a novel protein biomarker panel for active pediatric lupus nephritis.
Lupus nephritis (LN) is among the main determinants of poor prognosis in systemic lupus erythematosus (SLE). The objective of this study was to 1) isolate and identify proteins contained in the LN urinary protein signature (PS) of children with SLE; 2) assess the usefulness of the PS proteins for detecting activity of LN over time. Using surface-enhanced or matrix-assisted laser desorption/ionization time of flight mass spectrometry, the proteins contained in the LN urinary PS were identified. They were transferrin (Tf), ceruloplasmin (Cp), alpha1-acid-glycoprotein (AGP), lipocalin-type prostaglandin-D synthetase (L-PGDS), albumin, and albumin-related fragments. Serial plasma and urine samples were analyzed using immunonephelometry or ELISA in 98 children with SLE (78% African American) and 30 controls with juvenile idiopathic arthritis. All urinary PS proteins were significantly higher with active vs. inactive LN or in patients without LN (all p < 0.005), and their combined area under the receiver operating characteristic curve was 0.85. As early as 3 mo before a clinical diagnosis of worsening LN, significant increases of urinary Tf, AGP (both p < 0.0001), and L-PGDS (p < 0.01) occurred, indicating that these PS proteins are biomarkers of LN activity and may help anticipate the future course of LN.
Suzuki
Michiko
M
Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
Wiers
Kristina
K
Brooks
Elizabeth B
EB
Greis
Kenneth D
KD
Haines
Kathleen
K
Klein-Gitelman
Marisa S
MS
Olson
Judyann
J
Onel
Karen
K
O'Neil
Kathleen M
KM
Silverman
Earl D
ED
Tucker
Lori
L
Ying
Jun
J
Devarajan
Prasad
P
Brunner
Hermine I
HI
D000293:Adolescent; D000419:Albuminuria / Q000175:diagnosis; D001171:Arthritis, Juvenile / Q000175:diagnosis / Q000652:urine; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001798:Blood Proteins / Q000652:urine*; D016022:Case-Control Studies; D002570:Ceruloplasmin / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000097:blood / Q000652:urine; D054834:Lipocalins / Q000097:blood / Q000652:urine; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000175:diagnosis* / Q000652:urine; D008181:Lupus Nephritis / Q000175:diagnosis* / Q000209:etiology / Q000652:urine; D008297:Male; D009391:Nephelometry and Turbidimetry; D009961:Orosomucoid / Q000652:urine; D011237:Predictive Value of Tests; D011379:Prognosis; D011507:Proteinuria / Q000175:diagnosis* / Q000209:etiology / Q000652:urine; D012372:ROC Curve; D015203:Reproducibility of Results; D012709:Serum Albumin / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013997:Time Factors; D014168:Transferrin / Q000652:urine
D015415:Biomarkers; D001798:Blood Proteins; D054834:Lipocalins; D009961:Orosomucoid; D012709:Serum Albumin; D014168:Transferrin; D002570:Ceruloplasmin; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase