T cells recognize and kill a myriad of pathogen-infected or cancer cells using a diverse set of T cell receptors (TCR). The affinity of TCR to cognate antigen is of high interest in adoptive T cell transfer immunotherapy and antigen-specific T cell repertoire immune profiling because it is widely known to correlate with downstream T cell responses. Here, we introduce the in situ TCR affinity and sequence test (iTAST) for simultaneous measurement of TCR affinity and sequence from single primary CD8+ T cells in human blood. We demonstrate that the repertoire of primary antigen-specific T cells from pathogen inexperienced individuals has a surprisingly broad affinity range of 1000-fold composed of diverse TCR sequences. Within this range, samples from older individuals contained a reduced frequency of high affinity T cells compared to young individuals, demonstrating an age-related effect of T cell attrition that could cause holes in the repertoire. iTAST should enable the rapid selection of high affinity TCRs ex vivo for adoptive immunotherapy and measurement of T cell response for immune monitoring applications.
Nutcracker syndrome (NCS) is an extrinsic compression of the left renal vein (LRV) by the superior mesenteric artery (SMA) anteriorly and aorta posteriorly resulting in renal vascular congestion manifesting as hematuria, proteinuria, orthostatic hypotension, pain, or even renal dysfunction. Longstanding venous compression can encourage collateral drainage pathways through gonadal and pelvic veins, which may explain reported symptom and syndrome overlap with pelvic congestion syndrome. Diagnosis can be challenging and variable, frequently involving a combination of ultrasound Doppler, cross-sectional, and invasive imaging. Often, intravascular pressure measurements are required to prove a renocaval pressure gradient to aid in a definitive diagnosis. Conservative management is appropriate, especially in children, who tend to outgrow the disorder. In the interim, medical management with angiotensin converting enzyme inhibitors (ACEIs) is a useful therapy to manage orthostatic hypotension in the pediatric population.In adults, invasive therapies are more frequently pursued. These are aimed at relieving the extrinsic compression on the LRV. The standard of care is renal vein transposition, with renal autotransplantation reserved for recalcitrant cases. Endovascular stenting is a less invasive option. Laparoscopic placement of an exovascular stent is a newer therapy intended to minimize trauma to the LRV. In this review, we will discuss the clinical manifestations, diagnostic criterion, imaging features, and conservative and surgical therapies for this condition.
microRNA (miRNA) are short endogenous non-coding RNA that play a crucial role in post-transcriptional gene regulation and have been implicated in the initiation and progression of 160+ human diseases. Excellent analytical methods have been developed for the measurement of miRNA by mass spectrometry. However, interpretation of mass spectrometric data has been an incapacitating bottleneck in miRNA identification. This study details the development of MicroRNA MultiTool, a software for the identification of miRNA from mass spectrometric data. The software includes capabilities such as miRNA search and mass calculator, modified miRNA mass calculator, and miRNA fragment search. MicroRNA MultiTool bridges the gap between experimental data and identification of miRNA by providing a rapid means of mass spectrometric data interpretation.
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