Urine chemokines as biomarkers of human systemic lupus erythematosus activity.
The purpose of this study was to evaluate urine monocyte chemoattractant protein-1 (MCP-1) and IL-8 as biomarkers of SLE flare. Urine was collected every 2 mo from patients who were followed prospectively in the Ohio SLE Study. Renal and nonrenal flares were identified and MCP-1 and IL-8 were measured by specific ELISA in samples that were collected at flare. When available, MCP-1 and IL-8 were also measured in urine samples before and after flare. For comparison, MCP-1 and IL-8 were measured in the urine of healthy individuals and in renal and nonrenal SLE patients with stable disease activity (disease controls). Most patients were receiving maintenance immunosuppressive therapy before flare. At renal flare, mean urine MCP-1 (uMCP-1) was significantly greater than uMCP-1 at nonrenal flare and from healthy volunteers and renal disease controls. The level of uMCP-1 correlated with the increase in proteinuria at flare and was higher in patients with proliferative glomerulonephritis and in patients with impaired renal function. Urine MCP-1 was increased beginning 2 to 4 mo before flare. Patients who responded to therapy showed a slow decline in uMCP-1 over several months, whereas nonresponders had persistently high uMCP-1. In contrast, uIL-8 did not change with disease activity and was not elevated at renal or nonrenal flare compared with disease controls. In conclusion, uMCP-1 but not uIL-8 is a sensitive and specific biomarker of renal SLE flare and its severity, even in patients who receive significant immunosuppressive therapy. Persistently elevated uMCP-1 after treatment may indicate ongoing kidney injury that may adversely affect renal prognosis.
Rovin
Brad H
BH
Ohio State University, Nephrology Division, N210 Means Hall, 1654 Upham Drive, Columbus, OH 43210, USA. rovin-1@medctr.osu.edu
Song
Huijuan
H
Birmingham
Dan J
DJ
Hebert
Lee A
LA
Yu
Chack Yung
CY
Nagaraja
Haikady N
HN
D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000378:metabolism / Q000652:urine*; D018925:Chemokines / Q000378:metabolism / Q000652:urine*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism / Q000652:urine*; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis* / Q000652:urine*; D008297:Male; D008875:Middle Aged; D011336:Probability; D011379:Prognosis; D012016:Reference Values; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016482:Urinalysis
D015415:Biomarkers; D018932:Chemokine CCL2; D018925:Chemokines; D016209:Interleukin-8