Tag: biomarkers

T-Cells Could Identify ‘The Bends’ in Divers

Photo by USGS on Unsplash

A new study investigated genetic changes that occur in a serious condition affecting scuba divers — ‘the bends’ — and found that inflammatory genes and white blood cell activity are upregulated. The findings could lead to biomarkers that will help doctors to diagnose the condition more precisely.

The bends, more formally known as decompression sickness, is a potentially lethal condition that can affect divers. Symptoms include joint pain, a skin rash, and visual disturbances. In some patients, the condition can be severe, potentially leading to paralysis and death. The bends can also affect people working in submarines, flying in unpressurised aircraft or in spacewalks.

It has been studied for a long time: a 1908 paper correctly hypothesised that it involves bubbles of gas forming in the blood and tissue due to pressure decrease. Yet even after a century the precise mechanisms underlying the condition are not well understood. Animal studies have suggested that inflammatory processes may have a role in decompression sickness, but no-one had studied this in humans.

Nowadays, getting ‘the bends’ is rare as divers have well-established methods to mitigate risk, such as controlled ascents from the depths. Nevertheless, doctors have no means to test for the condition, if they do encounter it, and instead rely on observing symptoms and seeing whether patients respond to hyperbaric oxygen therapy.

To investigate decompression sickness, the researchers sampled the blood of divers who had been diagnosed with decompression sickness and also divers who had completed a dive without it. The blood samples were drawn at two times: within 8 hours of the divers emerging from the water, and 48 hours afterwards, when those divers with decompression sickness had undergone hyperbaric oxygen treatment. RNA sequencing analysis was done to measure gene expression changes in white blood cells.

“We showed that decompression sickness activates genes involved in white blood cell activity, inflammation and the generation of inflammatory proteins called cytokines,” explained Dr Nikolai Pace of the University of Malta, a researcher involved in the study. “Basically, decompression sickness activates some of the most primitive body defense mechanisms that are carried out by certain white blood cells.”

These genetic changes had diminished in samples from 48 hours after the dive, after the patients had been treated with hyperbaric oxygen therapy — an interesting finding. The results provide a first step towards a diagnostic test for decompression sickness, and may also reveal new treatment targets.

“We hope that our findings can aid the development of a blood-based biomarker test for human decompression sickness that can facilitate diagnosis or monitoring of treatment response,” said Prof Ingrid Eftedal of the Norwegian University of Science and Technology, who was also involved in the project. “This will require further evaluation and replication in larger groups of patients.”

Source: EurekaAlert!

Journal information: “Acute effects on the human peripheral blood transcriptome of decompression sickness secondary to scuba diving” Frontiers in Physiology, DOI: 10.3389/fphys.2021.660402

New Test Picks up Concussion Biomarkers in Saliva

A new test has been found to effectively pick up concussion biomarkers in the saliva of rugby players.

This paves the way for a non-invasive, easy-to-use pitch-side test to rapidly detect concussions for early treatment. Concussion is a serious problem in contact sports, with players such as college American Football athletes consistently underestimating its risk. Missing a concussion can have a range of consequences, from delayed recovery to more serious (albeit rare) injuries such as traumatic brain swelling.

Detecting concussions requires an assessment by a clinician of the signs and symptoms of the injury. However, recent advances in DNA sequencing technology have made it possible to use small non-coding RNAs (sncRNAs) as biomarkers in rapid tests. sncRNAs regulate the expression of different cellular proteins associated with various diseases, such as cancer and Alzheimer’s disease.

t is thought that since saliva can receive cellular signals directly from the cranial nerves in the mouth and throat, biomarkers from a brain injury would quickly show up.

A panel of 14 sncRNAs differentiated concussed players from those where traumatic brain injury had been suspected but ruled out, and from the comparison group, both straight after the game and 36–48 hours later.

Over two seasons, samples were collected before the rugby season began from 1028 players from the two elite professional tiers, and during standardised ‘gold standard’ head injury assessments at three time points—during the game, afterwards, and 36–48 hours later from 156 of these players .

The researchers also took saliva samples from a comparison group of 102 uninjured players, as well as 66 with muscle or joint injuries, and so had not had head injury assessments.

However, the researchers stressed that the observational study nature and design of this study cannot show that the biomarker test is any better than a gold standard clinical test for concussion.

“In community sport, [sncRNAs] may provide a non-invasive diagnostic test that is comparable in accuracy to the level of assessment available in a professional sport setting,” while the test could be added to current head injury evaluation protocols at the elite level,” they add.

And as the biology of concussion is still not fully understood, sncRNAs might help to shed light on the response to injury as this evolves over time, they suggest.

“The detection of signatures of concussion at early time points in saliva (a non-invasively sampled biofluid) presents both at the pitch side, and in primary care and emergency medicine departments, an opportunity to develop a new and objective diagnostic tool for this common clinical presentation,” they conclude.

As an addendum to their findings, they added: “A patented salivary concussion test is in the process of being commercialized as an over-the-counter test for elite male athletes.

“Meanwhile our research team aims to collect further samples from players in two elite men’s rugby competitions to provide additional data to expand the test and develop its use. This will guide the prognosis and safe return to play after concussion and further establish how the test will work alongside the head injury assessment process.”

The researchers plan to add more participants to the SCRUM study, such as female athletes and community players.
Source: Medical Xpress

Journal information: Valentina Di Pietro et al. Unique diagnostic signatures of concussion in the saliva of male athletes: the Study of Concussion in Rugby Union through MicroRNAs (SCRUM), British Journal of Sports Medicine (2021). DOI: 10.1136/bjsports-2020-103274

New Biomarker Can Predict Response to Checkpoint Inhibitor Therapy

A team of researchers at Roswell Park Comprehensive Cancer Center have identified a biomarker that could be used to predict how well immune checkpoint inhibitors will be tolerated.

Immune checkpoint inhibitors (ICI) activate anti-tumour defences either through the disruption of inhibitory interactions between antigen-presenting cells and T cells at so-called checkpoints or else through the stimulation of activating checkpoints. Not all patients can tolerate ICI well; side effects can be severe, including colitis, which is one of the most common.

Pre-treatment biomarkers are of limited value in predicting response to ICI. Tumour biopsy shortly after ICI therapy is started can provide helpful information, but is invasive and difficult to do in some certain cancers.
Uncovering blood-based biomarkers that reflect the change of the tumour microenvironment and can predict a patient’s response to ICIs could improve current treatment regimens significantly, Dr. Ito notes. The team’s previous research indicates that T cells with varying levels of the chemokine receptor CX3CR1 responded differently to ICI therapy.

Based on those findings, the researchers sought to test CX3CR1 as a T cell biomarker in ICI therapy. They found that ICI therapy is linked to increased frequency and clonality of some CX3CR1-positive T cells; that the frequency of these CD8+ T cells stays high during ICI therapy; and that there are many genomic similarities between CD8+ tumour-infiltrating lymphocytes and this subset of CX3CR1-positive T cells.

Fumito Ito, MD, PhD, FACS, explained: “Although ICIs revolutionized the cancer treatment for significant numbers of people, many cancer patients do not respond to them, and some develop severe toxicity.”

“Currently, we are in need of a better biomarker to predict the response to immunotherapy, which is part of standard treatment in advanced and metastatic lung cancer,” said Hongbin Chen, MD, PhD. “This study sheds light on a promising blood-based biomarker that is potentially very useful in identifying which patients with lung cancer are most likely to benefit from immunotherapy. We look forward to investigating its utility in further clinical research.”

Source: News-Medical.Net

Journal information: Yamauchi, T., et al. (2021) T-cell CX3CR1 expression as a dynamic blood-based biomarker of response to immune checkpoint inhibitors. Nature Communications.doi.org/10.1038/s41467-021-21619-0.

Plasma microRNAs as Biomarkers for Mild Brain Injury

Plasma microRNA could serve as biomarkers for the detection and diagnosis of mild traumatic brain injury, a recent study from the University of Eastern Finland (UEF) has found.

Mild traumatic brain injury is extremely difficult to detect as it is almost invisible to most imaging techniques, and visible signs in daily life may be masked by compensation for increased task difficulty.

Blood biomarkers can satisfy the demand for timely, accurate, easily accessible and affordable tests for mild traumatic brain injury. They are minimally invasive and can provide molecular information about the injury on an ongoing basis.

MicroRNAs (miRNAs) are non-coding sections of RNA that play a key role in gene expression. The researchers sequenced DNA in blood plasma taken from animal models subjected to mild and severe traumatic brain injury. They selected the miRNAs which showed the greatest potential for use as biomarkers for further analysis with polymerase chain reaction (PCR). They wanted biomarkers that were both sensitive and specific to traumatic brain injury in an animal model.

Dr Noora Puhakka, A. Virtanen Institute for Molecular Sciences, UEF, said, “We have been developing a suitable analysis and measurement method especially for miRNAs that can be found in small amounts in plasma, and this method is based on digital droplet PCR.

“Humans and animals share many identical miRNAs, and this makes them excellent candidates for translational studies, where results achieved in animal models are sought to be applied in humans. However, it has proven challenging to reproduce results from different studies and different sets of data. This is why assessing the quality of measurement methods, and reproducibility, is an extremely important part of biomarker research.”
The study a pair of possible biomarker candidates to diagnose mild traumatic brain injury both in the animal model and in human patients.  

“We found two interesting biomarkers in the animal model, the plasma miRNAs miR-9a-3p and miR-136-3p, which we then decided to analyse in blood samples taken from patients with traumatic brain injury. Elevated levels of these biomarkers allowed us to identify some of the patients who had experienced a mild traumatic brain injury,” Dr Puhakka explained.

“Both of these miRNAs are more abundant in the brain than in other tissues, and their elevated levels in plasma could possibly be due to brain injury and the level of its seriousness. However, further research in larger patient cohorts is still needed.”

Source: News-Medical.Net

Journal information: Gupta, S. D., et al. (2021) Plasma miR-9-3p and miR-136-3p as Potential Novel Diagnostic Biomarkers for Experimental and Human Mild Traumatic Brain Injury. International Journal of Molecular Sciences. doi.org/10.3390/ijms22041563.