Peripheral Blood B-Cell Subsets Frequency and Distribution and the BSF-2(IL-6) to CSIF:TGIF(IL-10) Ratio as Severity-Associated Signatures in Primary Open-Angle Glaucoma: A Case-Controlled Study.

Although primary open-angle glaucoma (POAG) is a major cause of blindness worldwide, patients' immune response and its relation to the disease course have not been fully unraveled in terms of analyses of circulating B-cell subsets, as well as the association of these subsets with the severity of POAG clinical features. SUBJECTS AND METHODS: Flow cytometry was used to determine B-cell subset frequencies from 30 POAG patients grouped by hierarchical cluster analysis or the mean deviation (MD) of the visual field (VF) and correlated with the patients' clinical and pathological data, as well as with BSF-2(IL-6) and CSIF:TGIF(IL-10), which were quantified in peripheral blood samples of patients and controls by ELISA. RESULTS: The total B-cell frequency was increased in the POAG group in comparison to the control group (n = 30). Frequencies of specific B-cell subsets, such as double-negative (DN) and naïve B-cell subsets, were increased in relation to the severity of the POAG disease. However, the unswitched memory B compartment subset decreased in the POAG group. Other non-typical B-cell subsets such as DN B cells also showed significant changes according to the POAG disease severity course. These differences allow us to identify POAG severity-associated inflammatory clusters in patients with specifically altered B-cell subsets. Finally, ocular parameters, biomarkers of inflammation, and other glaucoma-related or non-clinical scores exhibited correlations with some of these B-cell subpopulations. CONCLUSION: The severity of the POAG disease course is accompanied by changes in the B-cell subpopulation, namely, DN B cells. Furthermore, the existing relationship of the B-cell subset frequencies with the clinical and the inflammatory parameters BSF-2(IL-6), CSIF:TGIF(IL-10), and the BSF-2(IL-6) to CSIF:TGIF(IL-10) ratio suggests that these B lymphocyte cells could serve as potential molecular bio-markers for assessing POAG disease severity and/or progression.

Serum metabolomic profiles and semaphorin-3A as biomarkers of diabetic retinopathy progression.

Diabetic retinopathy (DR) is a typical microvascular complication of diabetes mellitus (DM) and it remains one of the leading causes of vision loss worldwide. Studies postulated that a distinct metabolic signature of DR exists and can be resolved from that of diabetes alone. Serum Semaphorin3A (Sema3A) levels have also been found to be correlated with the phenotypes of diabetic retinopathy. We aimed to analyze and identify serum metabolites and serum Sema3A levels that could be useful biomarkers of DR progression. This cross-sectional study included 45 type 2 diabetes (T2D) patients. Diabetic patients were divided into three groups based on the status of their complications: non-DR (NDR, n=15), non-proliferative DR (NPDR, n=15), and proliferative DR (PDR, n=15) groups. Serum metabolomic profiles of these patients were determined by using high-performance liquid chromatography-mass spectrometry (HPLC-MS), and serum Sema3A levels measured by ELISA. Metabolomics analysis revealed a set of metabolites that were altered in the serum of PDR patients as compared with NPDR and NDR groups. Among these metabolites total asymmetric dimethylarginine (ADMA) and Kynurenine were potential predictors of PDR patients. Significantly higher serum levels of Sema3A in PDR patients as compared with NPDR and NDR groups (p < 0.001), their serum levels were positively correlated with the central macular thickness (r= 0.952, p < 0.001) and negatively correlated with the superficial macular density (r=-0.952, p < 0.001). In conclusion, the metabolite signatures identified in this study and serum Sema3A levels could be proposed as biomarkers for DR development and progression in T2D patients. However, Sema3A was superior to metabolomics in the prediction of the severity of DR.

Maternal serum perlecan and ischemia modified albumin levels as biomarkers of preeclampsia severity.

Preeclampsia (PE) is a pregnancy disorder characterized by hypertension and end-organ damage. Reliable biochemical markers for diagnosis and prediction of PE severity can improve maternal health, and several of these markers have been suggested till now. The goal of our study was to evaluate maternal serum levels of Perlecan and Ischemia modified albumin (IMA) in PE patients, and to investigate their relationship with the severity. This study included 45 pregnant women, who were divided into three groups: mild PE (n=15), severe PE (n=10), and normal pregnant females (n=20) as a control group. Maternal serum levels of Perlecan and IMA were determined by the enzyme linked immunosorbent assay (ELISA). Preeclamptic women with severe features have significantly higher serum Perlecan and IMA levels than women with mild PE and control (P0.001 for both). Serum levels of Perlecan and IMA were significantly increased in patients with mild PE as compared with control (P0.001 for both). Serum Perlecan levels were positively correlated with systolic blood pressure (SBP), diastolic blood pressure (DBP), ALT, AST, creatinine, urea, uric acid, and proteinuria, but negatively correlated with platelet count and fetal birth weight. Serum IMA level was positively correlated with SBP, DBP, but negatively correlated with Albumin, and fetal birth weight. The receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of Perlecan and IMA in the prediction of PE severity. Serum Perlecan had greater sensitivity and lower specificity for severe PE than for mild PE. Serum IMA had greater sensitivity and lower specificity for severe PE than for mild PE. In conclusion, maternal serum Perlecan and IMA levels were biomarkers for monitoring PE and the increase in serum Perlecan levels was in accordance with the severity of PE. Also, Perlecan was superior to IMA as a predictor for PE severity.

Association of sTNFR1 and BNP Levels with Diminished Estimated Glomerular Filtration Rate in Type 2 Diabetic Egyptian Patients.

Renal dysfunction is a key risk factor for all-cause mortality in patients with type 2 diabetes (T2D). Special attention has been raised regarding the role of soluble tumor necrosis factor receptor1 (sTNFR1) and brain natriuretic peptide (BNP) in diabetic nephropathy (DN) since they play a crucial role in the pathogenesis of T2D complications. Elevated concentrations of sTNFR1and BNP were found to be associated with progression to end stage renal disease (ESRD) in T2D. We determined serum levels of sTNFR1 and BNP in T2D patients and correlated them with various clinical variables especially kidney function and urinary albumin creatinine ratio (UACR). This study included 30 patients with T2D who were divided into two groups according to estimated glomerular filtration rate (eGFR): group 1with (eGFR < 60 mL/min/1.73m²) and group 2 with (eGFR > 60 mL/min/1.73 m²). They were compared with 15 sexes and age matched healthy individuals as a control group. Serum levels of sTNFR1 and BNP were determined using ELISA. Serum levels of sTNFR1 and BNP were significantly higher in group1when compared with group 2 (P= 0.000, P= 0.000) and they were significantly higher in both group1 and group 2 as compared with control (P= 0.000, P= 0.000); (P= 0.000, P = 0.000) respectively. Both sTNFR1 and BNP levels showed significant negative correlation with eGFR (r = - 0.58, P = 0.000); (r= - 0.77, P= 0.000) respectively, and significant positive correlation with UACR (r= 0.84, P= 0.000); (r=0.80, P= 0.000) respectively. In conclusion, increased circulating levels of sTNFR1 and BNP were associated with loss of kidney function in T2D patients.