Characterization of T-Cell receptor repertoire in immunoglobulin a nephropathy.

Immunoglobulin A nephropathy (IgAN) is an autoimmune disease characterized by abnormal IgA deposition in glomerulus. Current diagnosis of IgAN still depends on renal biopsy, an invasive method that might increase the risk of clinical outcomes. Therefore, we aimed to explore the characteristics of T cell repertoire in IgAN from peripheral blood samples for identifying innovative diagnostic biomarkers. Herein, we included 8 IgAN patients, 25 non-IgAN patients, and 10 healthy controls in the study. A high-throughput immune repertoire sequencing was conducted to investigate the T-cell receptor beta-chain (TCRß) repertoire of peripheral blood. Characteristics of TCRß repertoire were assessed for these three distinct groups. A reduced TCRß repertoire diversity was observed in IgAN patients compared to non-IgAN and healthy individuals. A skewed distribution toward shorter TCRß complementarity determining region (CDR3) length was found in non-IgAN relative to IgAN patients. In addition, the differences in usages of five TRBV genes (TRBV5-4, TRBV6-4, TRBV12-1, TRBV16, and TRBV21-1) were identified between IgAN, non-IgAN, and healthy subjects. Of note, the TRBV6-4 gene, which is associated with mucosal-associated invariant T (MAIT) cells, exhibited higher usage in IgAN patients, suggesting potential importance of MAIT cells in IgAN. In short, our findings supported TCR repertoire characteristics as potential biomarkers for IgAN diagnosis.

Current Trends in Neoantigen-Based Cancer Vaccines.

Cancer immunotherapies are treatments that use drugs or cells to activate patients' own immune systems against cancer cells. Among them, cancer vaccines have recently been rapidly developed. Based on tumor-specific antigens referred to as neoantigens, these vaccines can be in various forms such as messenger (m)RNA and synthetic peptides to activate cytotoxic T cells and act with or without dendritic cells. Growing evidence suggests that neoantigen-based cancer vaccines possess a very promising future, yet the processes of immune recognition and activation to relay identification of a neoantigen through the histocompatibility complex (MHC) and T-cell receptor (TCR) remain unclear. Here, we describe features of neoantigens and the biological process of validating neoantigens, along with a discussion of recent progress in the scientific development and clinical applications of neoantigen-based cancer vaccines.

Simultaneous uterine and urinary bladder rupture in an otherwise successful vaginal birth after cesarean delivery.

Uterine rupture is the primary concern when a patient chooses a trial of labor after a cesarean section. Bladder rupture accompanied by uterine rupture should be taken into consideration if gross hematuria occurs. We report the case of a patient with uterine rupture during a trial of labor after cesarean delivery. She had a normal course of labor and no classic signs of uterine rupture. However, gross hematuria was noted after repair of the episiotomy. The patient began to complain of progressive abdominal pain, gross hematuria and oliguria. Cystoscopy revealed a direct communication between the bladder and the uterus. When opening the bladder peritoneum, rupture sites over the anterior uterus and posterior wall of the bladder were noted. Following primary repair of both wounds, a Foley catheter was left in place for 12 days. The patient had achieved a full recovery by the 2-year follow-up examination. Bladder injury and uterine rupture can occur at any time during labor. Gross hematuria immediately after delivery is the most common presentation. Cystoscopy is a good tool to identify the severity of bladder injury.

Analysis of collagen and glucose modulated cell growth within tissue engineered scaffolds.

The strategy of tissue engineering includes seeding cells onto porous scaffolds. The cellular construct is cultured in vitro for a period of time before transplantation for the patient. Because of the intrinsic complexity of biological systems, it is valuable to have models of simulation that can assess the culture conditions and optimize experiments. This work presents a mathematical model to account for the effects of glucose and type II collagen on chondrocyte growth under static culture conditions. Dependence of cell growth on collagen was assumed as a biphasic function of collagen quantity, whereby the cell growth rate increases and then decreases with increasing collagen content. Results from simulation were compared with experimental data in literature. The model was then applied to investigate the effects of cell seeding area, demonstrating the spatiotemporal evolution of cell distribution in scaffolds. Results show that the conventional uniform seeding method may not be a good way of gaining uniform and large cell number densities at the final stage of cultivation. A seeding mode that has cells reside initially in the middle area of scaffold was shown to be able to not only reduce the diffusion limitation of nutrients but also weaken the inhibiting impact of aggregated collagen on cell growth. Therefore the middle seeding mode may result in better cell amounts and uniformities for developing tissue engineered constructs.

Genome-wide detection of uniparental disomy in a fetus with intrauterine growth restriction using genotyping microarrays.

OBJECTIVE: To present the clinical and molecular features of a fetus with confined trisomy 16 mosaicism with maternal uniparental disomy (UPD), using various prenatal diagnostic techniques. MATERIALS AND METHODS: Chromosomal karyotyping was performed on samples of chorionic villi, amniotic fluid cells, amniotic membrane, umbilical cord, fetal skin, and placenta from a fetus with elevated nuchal translucency. Polymorphic short tandem repeat markers and Affymetrix single nucleotide polymorphism (SNP) mapping chips were used for molecular analyses. RESULTS: Karyotypes from chorionic villi and amniocytes showed 47,XX,+16 and 46,XX, respectively. Short tandem repeat markers on chromosome 16 suggested maternal UPD for chromosome 16. Affymetrix 10K SNP mapping chips were used to simultaneously confirm the difference in karyotypes between the placenta and amniocytes and to diagnose UPD for chromosome 16. Fetal ultrasonography and magnetic resonance imaging identified severe intrauterine growth restriction (IUGR). Autopsy revealed IUGR, incomplete lobulation of bilateral lungs, and malrotation of the intestines. The karyotypes of umbilical cord, fetal skin and amniotic membrane were 46,XX, and the trisomy 16 karyotype appeared to be confined to the placenta. CONCLUSION: UPD should be investigated as a possible etiology in all cases of unexplained IUGR. SNP microarrays can be useful for confirming this diagnosis.