A new open-access data tool, the 10,000 Immunomes Project (10KIP), offers researchers and clinical immunologists a standardized reference dataset of normal human immunity (Cell Reports 2018;25:513-22). Compiled using data from 83 publicly available studies involving 10,344 individuals which the investigators manually curated and harmonized, the 10KIP aims to accelerate discovery in immunology.
“We believe that integrating these datasets and presenting them as a fully open resource will pay dividends in terms of both basic research and the precision and robustness of ongoing translational efforts in immunology,” they wrote.
The data come from a diverse population, split evenly between men and women, and with racial and age diversity, including 1,000 subjects younger than age 18 and 1,300 older than age 65. The data were robust enough that the researchers were able to create a custom control group of women ages 18 to 40 to compare against 56 pregnant women who participated in a study of immunologic changes in pregnancy.
The authors standardized analyte names and units of measure, divided data by sample type, and corrected for sample dilutions. The inaugural dataset includes 10 data types in standardized tables, such as enzyme-linked immunosorbent assay (ELISA), multiplex ELISA, and flow cytometry and gene expression from both whole blood and peripheral blood mononuclear cells, as well as common blood tests like complete blood count, comprehensive metabolic panel, and fasting lipid profile. The authors deployed a model used in genomic analyses to compensate statistically for batch effects of multiplex ELISA data.
In analyzing the data, the researchers found that 20% of the 50 commonly measured cytokines, chemokines, and metabolic factors measured by multiplex ELISA differed significantly by race. For example, African-Americans have significantly higher levels of C-X-C motif chemokine 5 compared with other races. They also learned that 19 of these analytes vary significantly with age.
Analysis of serum cytokine measurements showed that some in this normal healthy population fall in a relatively tight range, but others, like C-C motif chemokine 4, have quite a wide range.
“These findings affirm the benefit of maintaining and growing a diverse common control population for the future of clinical and precision immunology,” according to the investigators.
Liquid Biopsy Detects More Targetable Mutations in Lung Cancer Than Tissue Biopsy Alone
A study designed to test the clinical utility of liquid biopsy in non-small cell lung cancer (NSCLC) found that in comparison to tissue biopsy this method—plasma-based circulating tumor DNA (ctDNA) next-generation sequencing (NGS)—nearly doubled the number of targetable mutations detected (JAMA Oncology 2018; doi:10.1001/jamaoncol.2018.4305). The findings “argue for incorporation of plasma-based genotyping into routine clinical management of patients with NSCLC,” according to the authors.
Of the 323 patients with metastatic NSCLC enrolled in this prospective cohort study conducted at the University of Pennsylvania (Penn), the investigators identified targetable mutations in 113 (35%), 94 of whom had ctDNA NGS testing only. Out of these 94, 31 (33%) had a targetable mutation detected and did not need to undergo tissue biopsy. In the 229 patients who underwent concurrent ctDNA NGS and tissue biopsy or who were unable to undergo tissue biopsy, the investigators identified by tissue biopsy a therapeutically targetable mutation in 47 (20.5%). However, adding ctDNA NGS increased to 82 (35.8%) the number of the targetable mutations identified.
The authors also reported that 85.7% (42) of patients who received targeted therapy based on ctDNA NGS achieved a complete or partial response, or maintained a stable disease status.
The clinical laboratory at Penn’s Center for Personalized Diagnostics conducted the tissue biopsy NGS starting with a 47-gene panel, and then using Agilent Technologies’ 153-gene panel. Guardant Health performed the ctDNA NGS using its Guardant360 panel, which increased from 70 genes to 73 during the study. The panels tested for therapeutically targetable driver and resistance mutations in EGFR, ALK, MET, and others.
“These findings show that liquid biopsy is increasing the detection of mutations we can target and improving patient outcomes, and when you combine that with the reality that liquid biopsy is less invasive for patients and, in some cases, may be the only option for patients, the clinical impact is very clear,” said co-lead author Charu Aggarwal, MD, MPH, an assistant professor of hematology-oncology at Penn.
Novel Point-of-Care Troponin Assay Offers AMI Rule-Out Discrimination Comparable to Lab-based Test
An observational study at an emergency department (ED) in New Zealand has found that a novel point-of-care (POC) cardiac troponin (cTn) assay produces results within 15 minutes of blood sampling and has comparable discriminatory ability to a lab-based high-sensitivity (hs) cTn assay for ruling out suspected acute myocardial infarction (AMI) after a single blood test (JAMA Cardiology 2018; doi:10.1001/jamacardio.2018.3368). The study was designed to assess the clinical accuracy of the new test, and these findings suggest that if the test were used in ED settings it might facilitate earlier decision-making, thereby expediting safe discharge of low-risk patients, according to the authors.
POC cTn tests render results quickly, but so far have lacked sufficient precision at low concentrations to enable clinicians to safely rule out AMI based on a single sample. For this reason, EDs still rely on lab-based hs-cTn assays, which, though accurate at low concentrations, have longer turnaround times.
The researchers evaluated a novel “high precision” POC cTn assay, the Abbott Point of Care TnI-Nx test. They emphasized that this assay has not yet been established as high-sensitivity, which requires a coefficient of variation <10% at the 99th percentile of a healthy population and that the assay measures cTn between the level of detection and the 99th percentile in at least 50% of healthy individuals.
In 354 patients assessed for suspected AMI, 16.1% actually experienced AMI. A TnI-Nx result <11 ng/L identified 56.7% as low risk, with both a sensitivity and negative predictive value (NPV) of 100%, respectively, and a TnI-Nx result <3 ng/L identified 43.5% of patients as low risk, also with sensitivity and NPV of 100%.
The authors speculated that this assay might be most useful in rural hospitals with limited rapid access to lab-based cTn assays.