Association Between Genetic Variation And Influenza Severity.

It is estimated that in the USA influenza -related deaths in recent years have ranged from 12,000 to 56,000. Factors like age, obesity, pregnancy and such chronic health conditions as asthma, chronic lung disease and heart disease are associated with an elevated risk of complications and death.

However, there are no proven genetic markers of influenza risk with an established mechanism of action. Interferon Induced Transmembrane Protein 3 (IFITM3) is an anti-viral protein that helps to block influenza infection of lung cells and to promote survival of the killer T cells that help clear the infection in the airways.

Image: A scanning electron micrograph of a CD8+ T cell engaging a virus.

(Photo courtesy of Dennis Kunkel).

A group of scientists collaborating with those at St. Jude Children's Research Hospital (Memphis, TN, USA) searched for other possible IFITM3 variants that correlated with gene expression, levels of the IFITM3 proteins and were common in influenza patients in the USA. The search led to an IFITM3 variant known as rs34481144. They checked 86 children and adults in Memphis with confirmed influenza infections and found two-thirds of patients with the most severe symptoms carried at least one copy of the newly identified high-risk IFITM3 variant. The high-risk variant was found in just 32% of patients with milder symptoms.

The team also found an association between the newly identified high-risk variant and severe and fatal influenza infections in 265 critically ill pediatric patients hospitalized in one of 31 intensive care units nationwide. The patients did not have health problems that put them at high risk for severe influenza. Of the 17 patients in this group who died from the infection, 14 carried at least one copy of the newly identified high-risk variant. Further study revealed how binding differed between the high-risk and protective variants. Those differences led to lower levels of the IFITM3 protein in individuals with two copies of the high-risk gene variant compared to other patients. The Memphis influenza patients also had fewer of the killer T cells in their upper airways. The study identifies a new regulator of IFITM3 expression that associates with CD8+ T cell levels in the airways and a spectrum of clinical outcomes.

Paul Thomas, PhD, an immunologist and corresponding author of the study, said, “A genetic marker of influenza risk could make a life-saving difference, particularly during severe influenza outbreaks, by helping prioritize high-risk patients for vaccination, drug therapy and other interventions. These results raise hopes that this newly identified IFITM3 variant might provide such a marker.” The study was published on July 17, 2017, in the journal Nature Medicine.

Source: labmedica

Screen Your Blood Cholesterol Levels For Your Heart Disease Risk!

Researchers have developed a first-of-its-kind rapid assay for measuring effectiveness of a patient’s high-density lipoprotein cholesterol (HDL-C) in cleaning up arterial cholesterol. This HDL-C function test could improve risk assessment and diagnosis, and help provide and monitor more personalized treatments for cardiovascular disease (CVD) patients.

Image: Research suggests a HDL-C function test could improve risk assessment and diagnosis,
and help provide and monitor more personalized treatments for CVD patients
(Photo courtesy of iStock).

While scientists have yet to fully elucidate how HDL-C helps protects against heart disease, one of its chief functions is thought to be mediating the removal of cholesterol from blood vessel walls. Recent studies have indicated that the ability of a patient’s HDL-C to do this – known as its cholesterol efflux capacity (CEC) – is a better gauge of CVD development than HDL-C levels on their own. This means, for example, that a patient with low levels of HDL-C but optimal CEC could be protected against heart disease to a greater degree than a patient with high levels of HDL-C but low CEC. However, the current standard research procedures for measuring CEC involve radioisotope-labeled cholesterol and cultured macrophages, making these methods too complex and time-consuming for clinical testing.

In this study, a team of researchers led by Amane Harada, PhD, of Sysmex Corporation (Kobe, Japan) and Ryuji Toh, MD, PhD, of Kobe University Graduate School of Medicine (Kobe, Japan) has developed a test for HDL-C function that is simple enough for clinical use. With a turnaround time of less than 6 hours, the test determines cholesterol uptake capacity (CUC) – the ability of HDL-C to accept additional cholesterol – which the researchers found correlates with CEC but is easier to measure. 

They evaluated their CUC test in 156 patients who had undergone revascularization (such as a stent or bypass) due to coronary artery disease and who had subsequently decreased their low-density lipoprotein cholesterol to a healthier level of less than 100 mg/dL. The study found that low CUC in these patients after treatment was significantly associated with the recurrence of coronary lesions. The researchers also determined that combining CUC with established CVD risk factors significantly improved the power of established factors to forecast which patients would redevelop heart disease.

If further trials validate this test, it could enable healthcare providers to use CUC in conjunction with HDL-C levels to better predict who is at risk for CVD onset or recurrence. This test could also be used to develop new treatments that increase CEC and to monitor their efficacy in patients.

“A more efficient enhancement of the atheroprotective functions of HDL may decrease the risk of atherosclerosis and [cardiovascular disease], although it has been difficult to develop therapeutic drugs with the expected effects,” wrote Harada and Toh in this paper, “We consider that this can be explained in part by the lack of a convenient assay system to evaluate HDL functionality without complicated or time-consuming procedures. In this respect, our cholesterol uptake assay provides a concise, accurate, and robust system for high-throughput analysis at low cost.”

The study, by Harada A et al, was published in the May 2017 issue of the Journal of Applied Laboratory Medicine.

Source: labmedica

Cardiac Biomarkers and Clinical Decision Making

New video discusses the importance of cardiac biomarkers

Click to watch video

In this video, hear from a former operating engineer at the White House who, despite an active lifestyle and basic good health, experienced sudden heart failure. In the context of his healthcare journey, the video highlights the role of cardiac biomarkers in clinical decision making and the diagnosis of a heart attack.

Diagnosed with advanced coronary artery disease, the patient underwent cardiac bypass surgery and was enrolled in a biomarker study during his postoperative course of treatment. “There’s no doubt that biomarkers have completely transformed how we care for our patients in cardiovascular medicine,” says the patient’s cardiologist.