Longitudinal assessment of urinary ALCAM, HPX, and PRDX6 in Korean patients with systemic lupus erythematosus: implications for disease activity monitoring and treatment response.

Introduction: This study aimed to demonstrate the potential of activated leukocyte cell adhesion molecule (ALCAM), hemopexin (HPX), and peroxiredoxin 6 (PRDX6) as urine biomarkers for systemic lupus erythematosus (SLE). Methods: Urine samples were collected from 138 Korean patients with SLE from the Ajou Lupus Cohort and 39 healthy controls (HC). The concentrations of urine biomarkers were analyzed using enzyme-linked immunosorbent assay kits specific for ALCAM, HPX, and PRDX6, respectively. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic utility, and Pearson's correlation analysis was conducted to assess the relationships between the disease activity and urine biomarkers. Results: Patients with SLE and patients with lupus nephritis (LN) showed significantly elevated ALCAM, HPX, and PRDX6 levels compared with HCs. ALCAM, HPX, and PRDX6 showed significant diagnostic values, especially for lupus nephritis (LN), with areas under the receiver operating characteristic curve for LN was 0.850 for ALCAM (95% CI, 0.778-0.921), 0.781 for HPX (95% CI, 0.695-0.867), and 0.714 for PRDX6 (95% CI, 0.617-0.812). Correlation analysis revealed that all proteins were significantly associated with anti-double stranded DNA antibody (ALCAM, r = 0.350, p < 0.001; HPX, r = 0.346, p < 0.001; PRDX6, r = 0.191, p = 0.026) and SLEDAI (ALCAM, r = 0.526, p < 0.001; HPX, r = 0.479, p < 0.001; PRDX6, r = 0.262, p = 0.002). Results from the follow-up of the three biomarker levels in these patients revealed a significant decrease, showing a positive correlation with changes in SLEDAI-2k scores (ALCAM, r = 0.502, p < 0.001; HPX, r = 0.475, p < 0.001; PRDX6, r = 0.245, p = 0.026), indicating their potential as indicators for tracking disease activity. Discussions: Urinary ALCAM, HPX, and PRDX6 levels have diagnostic value and reflect disease activity in Korean patients with SLE, emphasizing their potential for non-invasive monitoring and treatment response evaluation.

ALCAM and VCAM-1 as urine biomarkers of activity and long-term renal outcome in systemic lupus erythematosus.

OBJECTIVES: We investigated the cell adhesion molecules (CAMs) Vascular CAM 1 (VCAM-1) and Activated Leucocyte CAM (ALCAM) as urinary biomarkers in SLE patients with and without renal involvement. METHODS: Female SLE patients (n = 111) and non-SLE population-based controls (n = 99) were enrolled. We measured renal activity using the renal domain of the BILAG index and urine (U) and plasma (P) concentrations of soluble (s)VCAM 1 and U-sALCAM using ELISA. U-sCAM levels were next corrected by U-creatinine. RESULTS: U-sVCAM-1/creatinine and U-sALCAM/creatinine ratios were higher in SLE patients vs non-SLE controls (P < 0.001 for both), as well as in patients with active/low-active (BILAG A-C; n = 11) vs quiescent (BILAG D; n = 19) LN (P = 0.023 and P = 0.001, respectively). U-sALCAM/creatinine but not U-sVCAM-1/creatinine ratios were higher in patients with nephritis history (BILAG A-D; n = 30) vs non-renal SLE (BILAG E; n = 79) (P = 0.014). Patients with baseline U-sVCAM-1/creatinine ratios ≥75th percentile showed a 23-fold increased risk of a deterioration in estimated glomerular filtration rate by ≥25% during a 10-year follow-up (odds ratio: 22.9; 95% CI: 2.8, 189.2; P = 0.004); this association remained significant after adjustments for age, disease duration and organ damage. Traditional markers including anti-dsDNA antibodies did not predict this outcome. CONCLUSION: While high U-sVCAM-1 levels appear to reflect SLE disease activity, sALCAM might have particular importance in renal SLE. Both U-sVCAM-1 and U-sALCAM showed ability to distinguish SLE patients with active renal involvement from patients with quiescent or no prior nephritis. High U-sVCAM-1 levels may indicate patients at increased risk for long-term renal function loss.

Usefulness of urinary NMP22 to detect tumor recurrence of superficial bladder cancer after transurethral resection.

BACKGROUND: In a prospective study we compared the usefulness of urinary nuclear matrix protein 22 (NMP22) with that of urine cytology and other urinary markers in the monitoring of superficial bladder cancer after transurethral resection (TURBT). METHODS: The subjects were 156 patients, comprising 99 patients with superficial bladder cancer in whom TURBT was planned (untreated group) and 57 patients without tumors in the bladder who had been followed up after TURBT (follow-up group). RESULTS: Among the 156 patients, who were monitored for 11-26 months (median, 21 months), recurrence was observed in 51 patients (33.0%). At the time of recurrence, the sensitivities of NMP22, basic fetoprotein (BFP), and bladder tumor antigen (BTA) tests, and urine cytology were 18.6%, 23.3%, 9.3%, and 7.0%, respectively. The factors affecting the sensitivity of NMP22 were tumor size and urinary WBC. The size of recurrent tumors was significantly smaller (P<0.05) than that of the initial tumors. Based on receiver operating characteristic (ROC) curves calculated from the data of patients with recurrence, the ideal cutoff values at recurrence were recommended to be 5.0 U/ml for NMP22 and 6.0 ng/ml for BFP. Using these cutoff values, the sensitivities of NMP22 and BFP were 48.8% and 44.2%, respectively. CONCLUSIONS: Because the size of recurrent bladder tumors is usually smaller than that of the initial tumors, the cutoff values of urinary markers should be reduced to detect these tumors. We recommend 5.0 U/ml as a cutoff value of NMP22 for detection of recurrence of bladder tumor.

Urinary basic fetoprotein in the diagnosis and follow-up of patients with urothelial carcinoma.

BACKGROUND: Urothelial carcinoma is one of the most common malignant neoplasms of the urinary tract and is characterized by a high local recurrence rate. However, no specific and reliable tumor marker has been identified for the diagnosis and follow-up of patients with urothelial carcinoma. METHODS: Urinary basic fetoprotein (U-BFP) levels were measured by enzyme immunoassay in 119 patients with urothelial carcinoma, 64 patients with other urologic malignancies, 144 patients with benign diseases, and 166 healthy individuals to evaluate it clinical efficacy as a marker of urothelial carcinoma. The histologic logic localization of BFP was also studied. A cutoff value was set at 14 ng/mL based on the maximum diagnostic efficiency. RESULTS: The specificity and sensitivity of U-BEP for urothelial carcinoma was 91.7% and 58%, respectively. THe U-BFP positive rate increased significantly with the histologic grade. The U-BFP positive rate was higher in both Tis and T2-4 than in Ta, 1 disease. The U-BFP level exceeded the cutoff value before curative therapy in 32 patients; U-BFP was normalized in 97% of these patients within 2 weeks after therapy. There was a total of 11 recurrences and the U-BFP level returned to abnormally high levels in all instances. Histologic localization of U-BFP was demonstrated in the cytoplasm of the tumor cells in 80% of the patients. CONCLUSION: Based on these results, U-BFP is a potential tumor maker of urothelial carcinoma. In particular, the test could be used to monitor patients whose U-BFP value is positive before therapy.

Detection of novel fetal polypeptides in human amniotic fluid using two-dimensional gel electrophoresis.

We compared the two-dimensional polypeptide pattern of donor-matched samples of mid-gestational amniotic fluid and maternal plasma to identify fetally-derived polypeptides in the amniotic fluid. Ten major polypeptide groups, ranging in molecular mass from 14.6 to 225 Kilodaltons (K), were consistently present in amniotic fluid that were not detected in maternal plasma. Three of these polypeptide complexes have been identified: one is alphafetoprotein, the second is a cellular form of fibronectin, and the third is beta 2-microglobulin. We searched for the remaining seven polypeptides in fetal serum and urine to confirm their fetal origin. Urine contained two polypeptides at 30.5K and 25.5K with mobilities identical to species found in amniotic fluid; the 25.5K polypeptide was also present in cord serum. Possible sources for the remaining 5 components may be the fetal respiratory and gastrointestinal tracts, integument, membranes (amnion and chorion) or the uterus. In addition, developmental changes in amniotic fluid polypeptides were studied by comparing samples obtained at mid-gestation and at term. Three proteins characteristic of mid-gestational amniotic fluid with masses of 185.8K, 38.2K and 25.4K were not detected or were present only at trace levels at term; and new polypeptide groups at approximately 51K, and 18K were observed in late gestation.

Placental antigens and fetoproteins in the urine of rats - indicators of resorption of conceptuses.

Placenta-specific antigens and alpha-fetoprotein were detected in the urine of rats with induced abnormal pregnancies. Moreover, in those cases, in which the presumptive diagnosis of intrauterine fetal death or resorption was made, urinary excretion of placental antigens persisted for at least 5 days.

Excretion of alpha-foetoprotein in the urine of pregnant rats and hepatoma-bearing animals.

Urine of normal rats, pregnant animals and animals bearing chemically induced hepatoma was tested with antisera to foetoproteins by the double immunodiffusion technique. Antigens were not detected in the urine of normal rats. Alpha-foetoprotein was demonstrated in the urine of pregnant rats and hepatomabearing animals.

Human alpha fetoprotein in body fluids.

Human alpha fetoprotein (AFP) has been detected by the agar double diffusion method in ascitic fluid, cerebrospinal fluid (CSF) and bile, from fetuses, neonates and patients with AFP seropositive hepatocellular carcinoma. AFP was detected in the meconium and faeces of fetuses and neonates respectively. The protein was not detected in the amniotic fluid nor the pericardial fluid. It was found in the urine in only two fetuses that had concomittant renal disease. It was not detected in breast milk of lactating females. When metastases occurred in the lung from a hepatocellular carcinoma producing AFP, the pleural effusions sometimes contained AFP. The concentrations of AFP in the serum and in the other body fluids were about the same. This indicates that other body fluids can be used for the diagnosis of hepatocellular carcinoma.