ABSTRACT
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.
ABSTRACT
Introduction: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are considered for patients with peritoneal metastasis (PM). However, patients selection that relies on conventional prognostic factors is not yet optimal. In this study, we performed whole exome sequencing (WES) to establish tumor molecular characteristics and expect to identify prognosis profiles for PM management. Methods: In this study, blood and tumor samples were collected from patients with PM before HIPEC. Tumor molecular signatures were determined using WES. Patient cohort was divided into responders and non-responders according to 12-month progression-free survival (PFS). Genomic characteristics between the two cohorts were compared to study potential targets. Results: In total, 15 patients with PM were enrolled in this study. Driver genes and enriched pathways were identified from WES results. AGAP5 mutation was found in all responders. This mutation was significantly associated with better OS (p = 0.00652). Conclusions: We identified prognostic markers that might be useful to facilitate decision-making before CRS/HIPEC.
