We evaluated 22 paired maternal and cord sera regarding the presence of IgG and IgG subclasses against purified Escherichia coli LPS O6, O16 and O111 employing ELISA for titre and avidity analysis, isoelectric focusing associated with affinity-blotting for spectrotypic analysis, and the Western-blotting technique for recognition of the various bands in lipopolysaccharide (LPS). Levels of anti-LPS IgG antibodies in cord sera were equivalent to their respective maternal sera, showing a significant correlation (P < 0.0001). IgG1 antibody levels were higher in cord sera than in maternal sera (P < 0.005 for anti-O111, P < 0.05 for anti-O16 and P < 0.02 for anti-O6). Cord IgG2 antibody levels were not different from the maternal levels (P > 0.1). The levels of IgG3 and IgG4 were undetectable. The avidity of anti-O6 and anti-O111 IgG in 10 cord sera showed an extremely significant correlation with maternal antibody avidity (P < 0.0001). Identical patterns of recognition were found in the paired samples analysed by Western blotting. Most of the serum samples recognized the O-repetitive chains and also the region corresponding to core and lipid A. Although the antibody spectrotypes varied among individuals, paired cord and maternal serum samples showed identical patterns. Our findings suggest the occurrence of placental transfer of IgG antibodies against LPS O6, O16 and O111, mainly involving the IgG1 or IgG2 subclasses.
Rationale & Objective In antiPLA2R membranous nephropathy (MN), there is controversy whether spontaneous remission (SR) can be predicted using a single titer, or assessing the dynamic changes anti-PLA2Rab titers. The study objective was to identify the optimal dynamics of anti-PLA2Rab titer to predict SR in MN Patients and Method 127 nephrotic patients with antiPLA2R-MN were prospectively followed-up for 6 months under conservative treatment. Anti-PLA2Rab and proteinuria were assessed at diagnosis and monthly thereafter. The primary end-point (PEP) was the reduction of proteinuria ≥50% at 6 months. Logistic models with baseline and evolutive antiPLA2Rab titers were developed to predict the PEP. Results 28 patients (22%) reached the PEP. These patients were more frequently female and had significantly lower baseline proteinuria and anti-PLA2Rab titers. An anti-PLA2R titer ≤ 97.5 RU/mL at diagnosis, had a sensitivity of 71% and a specificity of 81% to predict the PEP. The model including baseline anti-PLA2Rab and a reduction ≥ 15% at 3 months predicted the PEP with a sensitivity of 93% and a specificity of 80%, with an AUC significantly higher than that obtained with relative changes of proteinuria at the same period of time [0.95 (95%CI: 0.91-0.98) vs 0.79 (95%CI: 0.70-0.88) respectively p: 0.0013]. Conclusions combining the baseline antiPLA2Rab titers with their relative changes at 3 months after diagnosis, gives the earliest prediction for achieving a reduction of urinary protein excretion ≥50% at 6 months in MN, thereby shortening the observation period currently recommended to make individualized decisions to start immunosuppressive therapy.
Vitamin D (VD) deficiency has been associated with cancer and diabetes. Insulin signaling through the insulin receptor (IR) stimulates cellular responses by activating the PI3K/AKT pathway. PTEN is a tumor suppressor and a negative regulator of the pathway. Its absence enhances insulin signaling leading to hypoglycemia, a dangerous complication found after insulin overdose. We analyzed the effect of VD signaling in a model of overactivation of the IR. We generated inducible double KO (DKO) mice for the VD receptor (VDR) and PTEN. DKO mice showed severe hypoglycemia, lower total cholesterol and increased mortality. No macroscopic tumors were detected. Analysis of the glucose metabolism did not show clear differences that would explain the increased mortality. Glucose supplementation, either systemically or directly into the brain, did not enhance DKO survival. Lipidic liver metabolism was altered as there was a delay in the activation of genes related to β-oxidation and a decrease in lipogenesis in DKO mice. High-fat diet administration in DKO significantly improved its life span. Lack of vitamin D signaling increases mortality in a model of overactivation of the IR by impairing lipid metabolism. Clinically, these results reveal the importance of adequate Vitamin D levels in T1D patients.
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