Molecular characterization of β-trace protein in human serum and urine: A potential diagnostic marker for renal diseases

Abstract

We have isolated β-trace protein from cerebrospinal fluid, serum, plasma, and urine samples of normal volunteers and sera and hemofiltrate of patients with chronic renal failure. Blood-derived and urinary β-trace have significantly higher molecular weights than their cerebrospinal fluid counterpart, the amino acid sequences being identical. Oligosaccharide structural analysis revealed these molecular weight differences to be due to different N-glycosylation, β-Trace from hemofiltrate and urine has larger sugar chains and concurrently significantly higher sialylation than cerebrospinal fluid-β-trace which bears truncated 'brain-type' oligosaccharide chains (published previously), β-Trace concentrations mere about 40 ng/ml for normal sera and plasma, 2000-6000 ng/ml were measured in sera of dialysis patients whereas in normal human cerebrospinal fluid, β-trace concentration was about 8000 ng/ ml. A reduced amount of 900 ng/ml was found in a single case of hydrocephalus cerebri. The sialylated glycoforms of β-trace detected in the blood are presumably derived from resorbed cerebrospinal fluid protein whereas β-TP-molecules bearing asialo-oligosaccharides are absent due to their hepatic clearance. The residual, sialylated β-TP-species are probably eliminated from the blood via the kidney. This physiological clearance mechanism for the sialylated glycoforms is disturbed in hemodialysis patients resulting in about 100-fold elevated serum concentrations. These results let us suggest β-trace may become a useful novel diagnostic protein in renal diseases.