Elevated urinary VCAM-1, P-selectin, soluble TNF receptor-1, and CXC chemokine ligand 16 in multiple murine lupus strains and human lupus nephritis.
In an effort to identify potential biomarkers in lupus nephritis, urine from mice with spontaneous lupus nephritis was screened for the presence of VCAM-1, P-selectin, TNFR-1, and CXCL16, four molecules that had previously been shown to be elevated in experimental immune nephritis, particularly at the peak of disease. Interestingly, all four molecules were elevated approximately 2- to 4-fold in the urine of several strains of mice with spontaneous lupus nephritis, including the MRL/lpr, NZM2410, and B6.Sle1.lpr strains, correlating well with proteinuria. VCAM-1, P-selectin, TNFR-1, and CXCL16 were enriched in the urine compared with the serum particularly in active disease, and were shown to be expressed within the diseased kidneys. Finally, all four molecules were also elevated in the urine of patients with lupus nephritis, correlating well with urine protein levels and systemic lupus erythematosus disease activity index scores. In particular, urinary VCAM-1 and CXCL16 showed superior specificity and sensitivity in distinguishing subjects with active renal disease from the other systemic lupus erythematosus patients. These studies uncover VCAM-1, P-selectin, TNFR-1, and CXCL16 as a quartet of molecules that may have potential diagnostic significance in lupus nephritis. Longitudinal studies are warranted to establish the clinical use of these potential biomarkers.
Wu
Tianfu
T
Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, TX 75235, USA.
Xie
Chun
C
Wang
Hong W
HW
Zhou
Xin J
XJ
Schwartz
Noa
N
Calixto
Sergio
S
Mackay
Meggan
M
Aranow
Cynthia
C
Putterman
Chaim
C
Mohan
Chandra
C
D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6 / Q000097:blood / Q000652:urine*; D019743:Chemokines, CXC / Q000097:blood / Q000652:urine*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008181:Lupus Nephritis / Q000097:blood / Q000473:pathology / Q000652:urine*; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000097:blood / Q000473:pathology / Q000652:urine; D051116:Receptors, Scavenger / Q000097:blood; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood / Q000652:urine*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood / Q000652:urine*
D015415:Biomarkers; C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; D019743:Chemokines, CXC; C498926:Cxcl16 protein, mouse; D051116:Receptors, Scavenger; D047888:Receptors, Tumor Necrosis Factor, Type I; C506236:Tnfrsf1a protein, mouse; D019010:Vascular Cell Adhesion Molecule-1