Defective Tamm-Horsfall Protein in Patients With Interstitial Cystitis

Abstract

Normal urinary Tamm-Horsfall protein shows a urothelial cytoprotective effect against potentially toxic compounds in urine that may injure the urothelium and cause bladder disease. One such disease is interstitial cystitis. In patients with interstitial cystitis this protective effect is decreased. We hypothesized that a difference in Tamm-Horsfall protein in patients with interstitial cystitis exists that may be involved in disease pathogenesis. Using enzyme-linked immunosorbent assay the urinary Tamm-Horsfall protein concentration was determined in patients with interstitial cystitis and control subjects. Sialic acid content was measured by high performance liquid chromatography based assay. The structure of the protein glycosylation chains was analyzed using matrix assisted laser desorption/ionization-time of flight mass spectrometry. The mean Tamm-Horsfall protein concentration was not significantly different in patients with interstitial cystitis and controls (28.8 vs 28.2 mg/l urine and 36.8 vs 36.7 microg/mg creatinine, respectively, p = 0.6). The total mean sialic acid content of Tamm-Horsfall protein was almost 2-fold lower in 22 patients with interstitial cystitis compared with that in 20 controls (46.3 +/- 4.3 vs 75.3 +/- 4.1 nmol sialic acid per mg Tamm-Horsfall protein, respectively, p <0.0001). On matrix assisted laser desorption/ionization-time of flight mass spectrometry N-glycans released from Tamm-Horsfall protein revealed lower molecular weight di-antennary N-glycan structures and a resulting decrease in the number of terminal sialic acid residues in 10 patients with interstitial cystitis relative to those in 10 controls. Tamm-Horsfall protein is qualitatively different in patients with interstitial cystitis compared to controls. These data suggest that altered Tamm-Horsfall protein may be involved in interstitial cystitis pathogenesis and it may be useful for clinical diagnosis.