Gender Differences in Developing Biomarker-Based Major Depressive Disorder Diagnostics.

The identification of biomarkers associated with major depressive disorder (MDD) holds great promise to develop an objective laboratory test. However, current biomarkers lack discriminative power due to the complex biological background, and not much is known about the influence of potential modifiers such as gender. We first performed a cross-sectional study on the discriminative power of biomarkers for MDD by investigating gender differences in biomarker levels. Out of 28 biomarkers, 21 biomarkers were significantly different between genders. Second, a novel statistical approach was applied to investigate the effect of gender on MDD disease classification using a panel of biomarkers. Eleven biomarkers were identified in men and eight in women, three of which were active in both genders. Gender stratification caused a (non-significant) increase of Area Under Curve (AUC) for men (AUC = 0.806) and women (AUC = 0.807) compared to non-stratification (AUC = 0.739). In conclusion, we have shown that there are differences in biomarker levels between men and women which may impact accurate disease classification of MDD when gender is not taken into account.

Proteomic Analysis of Urine from California Sea Lions ( Zalophus californianus): A Resource for Urinary Biomarker Discovery.

Urinary markers for the assessment of kidney diseases in wild animals are limited, in part, due to the lack of urinary proteome data, especially for marine mammals. One of the most prevalent kidney diseases in marine mammals is caused by Leptospira interrogans, which is the second most common etiology linked to stranding of California sea lions ( Zalophus californianus). Urine proteins from 11 sea lions with leptospirosis kidney disease and eight sea lions without leptospirosis or kidney disease were analyzed using shotgun proteomics. In total, 2694 protein groups were identified, and 316 were differentially abundant between groups. Major urine proteins in sea lions were similar to major urine proteins in dogs and humans except for the preponderance of resistin, lysozyme C, and PDZ domain containing 1, which appear to be over-represented. Previously reported urine protein markers of kidney injury in humans and animals were also identified. Notably, neutrophil gelatinase-associated lipocalin, osteopontin, and epidermal fatty acid binding protein were elevated over 20-fold in the leptospirosis-infected sea lions. Consistent with leptospirosis infection in rodents, urinary proteins associated with the renin-angiotensin system were depressed, including neprilysin. This study represents a foundation from which to explore the clinical use of urinary protein markers in California sea lions.

Resistin as a potential marker of renal disease in lupus nephritis.

Systemic lupus erythematosus (SLE) and lupus nephritis (LN) have strong concomitance with cardiovascular disease that cannot be explained fully by typical risk factors. We examined the possibility that serum or urine expression of adipokines may act as biomarkers for LN, as these proteins have been associated previously with cardiovascular disease as well as SLE. Antibody arrays were performed on serum and urine from lupus patients and matched controls using a cross-sectional study design. From the initial array-based screening data of 15 adipokines, adiponectin, leptin and resistin were selected for validation by enzyme-linked immunosorbent assay (ELISA). Correlations were determined between adipokine expression levels and measures of disease activity or lupus nephritis. The expression of adiponectin and resistin was increased in both sera and urine from LN patients, while leptin was increased in LN patient sera, compared to matched controls. Serum resistin, but not urine resistin, was correlated with measures of renal dysfunction in LN. Serum resistin expression may be useful as a marker of renal dysfunction in patients with LN, although longitudinal studies are warranted. Further studies are necessary to determine if resistin has functional consequences in LN.

A novel ultra-sensitive enzyme immunoassay for soluble human insulin receptor ectodomain and its measurement in urine from healthy subjects and patients with diabetes mellitus.

OBJECTIVE: For the early identification of patients at risk of developing diabetes mellitus, and to prevent the onset of diabetes by performing dietary counseling and exercise guidance, we have developed an ultra-sensitive immune complex transfer enzyme immunoassay (ICT-EIA) to measure soluble human insulin receptor ectodomain (sIRalpha) in urine which is collected non-invasively. DESIGN AND METHODS: We developed ICT-EIA for sIRalpha and measured urinary sIRalpha from 106 healthy volunteers, 35 obese volunteers and 42 patients with diabetes. RESULTS: The detection limit of ICT-EIA (0.04 pg/mL), using a urine sample of as little as 100 microL, was a few hundred-fold higher than that of conventional ELISA. Using ICT-EIA, the urinary sIRalpha level in patients with diabetes (9.7+/-20.1 pg/mg creatinine) was significantly higher than those in healthy volunteers (1.4+/-0.9; P<0.001). CONCLUSION: ICT-EIA for sIRalpha may be useful as a good marker for evaluating diabetes risk.

Plasma and urine levels of resistin and adiponectin in chronic kidney disease.

BACKGROUND: Subjects with chronic kidney disease (CKD) have an increased risk of developing coronary atherosclerosis. Adipocyte hormones, resistin and adiponectin are implicated in insulin resistance and atherosclerosis. However, few studies in the literature address the role of adipocyte hormones in CKD. The aim of this study was to compare the levels of resistin, adiponectin and other inflammatory markers in subjects with CKD with those of the control subjects. MATERIALS AND METHODS: In a cross-sectional study, we measured basal metabolic panel, fasting lipid panel and levels of glucose, resistin, adiponectin, insulin, C-reactive protein (CRP) and TNF-alpha in 43 subjects with CKD compared with those of 34 control subjects. We also measured the resistin and adiponectin levels in urine samples (16). RESULTS: Subjects with CKD have increased insulin levels and insulin resistance index (IRI). Compared with controls, subjects with CKD had increased levels of resistin (5.12+/-3.2 vs.7.5+/-5.9; p<0.05), CRP (1.7+/-2.2 vs. 5.97+/-6.0; p<0.0005), and TNF-alpha (3.4+/-2.0 vs. 5.2+/-3.5; p<0.005). Resistin levels correlate with CRP and TNF-alpha, even with BMI as a covariate. Although 60% of subjects with CKD have CAD, e plasma levels of adiponectin were not decreased in subjects with CKD compared with controls (17.02+/-9.8 vs. 16.40+/-9.0 with p value 0.78). Urinary adiponectin levels correlate inversely with GFR (r=-0.4; p<0.05) and plasma adiponectin levels (r=0.9; p<0.0001). CONCLUSIONS: Subjects with CKD had normal levels of plasma adiponectin despite the adverse metabolic environment for CAD. In addition, this study demonstrates the relationship between resistin and TNF-alpha in subjects with CKD and suggests that resistin may play a role in the sub-clinical inflammation associated with CKD, suggesting that adiponectin clearance may be decreased as shown by the inverse correlation of urinary adiponectin with GFR.