Findings could lead to new clinical laboratory tests to screen for individuals with increased risk of blood transfusion complications
Pathologists and clinical laboratory scientists who understand the complexities of blood typing from one human to another will be interested to learn that a 50 year-old mystery has brought about an exciting new discovery—a new human blood group.
British and Israeli scientists led by the UK’s NHS Blood and Transplant (NHSBT) and the University of Bristol discovered the meaning behind a missing protein molecule found in a pregnant woman five decades ago. This anomaly has now been given its own blood group identification called MAL, according to a University of Bristol new release.
“Some people can lack this blood group due to the effect of illness, but the rare inherited form of the AnWj-negative phenotype has only been found in a handful of individuals—though due to this discovery it will now be easier to find others in the future,” the news release notes.
This is important because receiving mismatched blood can be fatal.
“AnWj is a high-prevalence red blood cell (RBC) antigen in the ISBT 901 series. Only nine reports of anti-AnWj have been published since it was first documented in 1972,” according to a 2012 article published by the American Association of Blood Banks, now known as the Association for the Advancement of Blood and Biotherapies (AABB).
For even the small proportion of the population with this new blood group, diagnosing its presence can have a major impact while preventing unwanted harm.
“The work was difficult because the genetic cases are very rare. We would not have achieved this without exome sequencing, as the gene we identified wasn’t an obvious candidate and little is known about Mal protein in red cells,” said Louise Tilley, PhD, Senior Research Scientist, IBGRL Red Cell Reference at NHS Blood and Transplant, in the news release.
“The genetic background of AnWj has been a mystery for more than 50 years, and one which I personally have been trying to resolve for almost 20 years of my career,” said Louise Tilley, PhD (above), Senior Research Scientist, IBGRL Red Cell Reference at NHS Blood and Transplant, in the news release. “It represents a huge achievement, and the culmination of a long term effort, to finally establish this new blood group system and be able to offer the best care to rare, but important, patients,” she added. Clinical laboratory scientists involved in blood banking will want to keep updated as further research into this new blood group is published. (Photo copyright: NHS Blood and Transplant.)
Unraveling the Mystery
In 1972, scientists were stumped by a pregnant woman with a blood sample that was “mysteriously missing a surface molecule found on all other known red blood cells at the time,” Science Alert reported. The AnWj antigen that was missing in that patient’s blood is present in 99.9% of human blood samples.
“Researchers found that the AnWj antigen is carried on the Mal protein. While illness can cause some people to lose the AnWj antigen, inherited cases of the AnWj-negative phenotype are extremely rare. Using whole exome sequencing on five genetically AnWj-negative individuals, researchers confirmed that, in these cases, the participants lacked the antigen due to homozygous deletions in the MAL gene,” an AABB news release stated.
The researchers named the group with the missing antigen the MAL blood group (short for Myelin and Lymphocyte Protein) which is where the antigen resides.
Genetic sequencing enabled the scientists to locate the gene when they “inserted the normal MAL gene into blood cells that were AnWj-negative. This effectively delivered the AnWj antigen to those cells,” Science Alert noted.
Mutated MAL genes result in the AnWj-negative blood type. The team discovered three patients with the blood type and no mutation, “Suggesting that sometimes blood disorders can also cause the antigen to be suppressed,” Science Alert added. The researchers also discovered that AnWj isn’t present in newborns but arrives sometime after they are born.
“Interestingly, all the AnWj-negative patients included in the study shared the same mutation. However, no other cell abnormalities or diseases were found to be associated with this mutation,” Science Alert said.
The discovery that “the Mal protein is responsible for binding AnWj antibodies” could lead to new clinical laboratory tests to screen for patients at risk from blood transfusions, AABB noted in its news release.
Facing the Challenge
Scientists had to overcome many challenges to uncover the details of this blood type. The complexity of the protein further hindered their efforts.
“MAL is a very small protein with some interesting properties which made it difficult to identify, and this meant we needed to pursue multiple lines of investigation to accumulate the proof we needed to establish this blood group system,” said Tim Satchwell, PhD, senior lecturer and cell biologist at the University of the West of England, in the University of Bristol news release.
“Resolving the genetic basis for AnWj has been one of our most challenging projects,” Nicole Thornton, head of IBGRL Red Cell Reference at NHSBT told the AABB. “There is so much work that goes into proving that a gene does actually encode a blood group antigen, but it is what we are passionate about, making these discoveries for the benefit of rare patients around the world.”
It’s hard to pinpoint how many individuals will benefit by testing for the blood group, Tilley told the BBC. Nevertheless, “the NHSBT is the last resort for about 400 patients across the world each year,” the BBC reported.
While more research needs to be done, the initial discovery is promising and may lead to new clinical laboratory tests to identify individuals who could be severely harmed should they receive the wrong blood type during a transfusion.
Study shows that computer analysis of clinical laboratory test results has improved greatly in recent years
Studies using “big data” continue to show how combining different types of healthcare information can generate insights not available with smaller datasets. In this case, researchers at Washington University School of Medicine (WashU Medicine), St. Louis, Mo., determined that—by using the results from nine different types of clinical laboratory tests—they could correlate those test results to younger people who had “aged faster” and had developed cancer earlier than usual, according to CNN.
“Accumulating evidence suggests that the younger generations may be aging more swiftly than anticipated, likely due to earlier exposure to various risk factors and environmental insults. However, the impact of accelerated aging on early-onset cancer development remains unclear,” said Ruiyi Tian, PhD candidate at WashU Medicine’s Yin Cao Lab in an American Association for Cancer Research (AACR) news release.
The scientists presented their findings, which have not yet been published, at the AACR’s annual meeting held in April. Tian and the other researchers “hypothesized that increased biological age, indicative of accelerated aging, may contribute to the development of early-onset cancers, often defined as cancers diagnosed in adults younger than 55 years. In contrast to chronological age—which measures how long a person has been alive—biological age refers to the condition of a person’s body and physiological processes and is considered modifiable,” AACR noted in a news release.
“We all know cancer is an aging disease. However, it is really coming to a younger population. So, whether we can use the well-developed concept of biological aging to apply that to the younger generation is a really untouched area,” Yin Cao, ScD MPH (above), associate professor of surgery and associate professor of medicine at Washington University School of Medicine in St. Louis, and senior author of the study, told CNN. Analysis of clinical laboratory test results using computer algorithms continues to show value for new research into deadly diseases. (Photo copyright: Washington University.)
Lab Tests Share Insights about Aging
To acquire the data they needed for their research, the WashU Medicine scientists turned to the UK Biobank, a biomedical and research resource with genetic and health information on half a million UK residents.
The researchers reviewed the medical records of 148,724 biobank participants, age 37 to 54, focusing on nine blood-based biomarkers that “have been shown to correlate with biological age,” CNN reported. Those biomarkers are:
White blood cells: counts in “the high end of the normal range” may relate to “greater age.”
According to CNN, the researchers “plugged” the nine values into an algorithm called PhenoAge. Using the algorithm they compared the biological ages with each person’s actual chronological age to determine “accelerated aging.” They then consulted cancer registries to capture data on those in the study who were diagnosed with cancer before age 55. They found 3,200 cases.
Young Adults Aging Faster than Earlier Generations
According to the AACR news release, the WashU Medicine study found that:
“Individuals born in or after 1965 had a 17% higher likelihood of accelerated aging than those born between 1950 and 1954.
“Each standard deviation increase in accelerated aging was associated with a 42% increased risk of early-onset lung cancer, a 22% increased risk of early-onset gastrointestinal cancer, and a 36% increased risk of early-onset uterine cancer.
“Accelerated aging did not significantly impact the risk of late-onset lung cancer (defined here as cancer diagnosed after age 55), but it was associated with a 16% and 23% increased risk of late-onset gastrointestinal and uterine cancers, respectively.”
“We speculate that common pathways, such as chronic inflammation and cellular senescence, may link accelerated aging to the development of early-onset cancers,” the study’s principal investigator Yin Cao, ScD, MPH, associate professor of surgery and associate professor of medicine at WashU Medicine, told The Hill.
“Historically, both cancer and aging have been viewed primarily as concerns for older populations. The realization that cancer, and now aging, are becoming significant issues for younger demographics over the past decades was unexpected,” Tian told Fox News.
More Screenings, Further Analysis
The study’s results may suggest a change in clinical laboratory screenings for younger people.
In future studies, WashU Medicine scientists may aim to include groups of greater diversity and explore why people are aging faster and have risk of early-onset cancers.
“There is room to improve using better technologies. Looking at the bigger picture, the aging concept can be applied to younger people to include cancers, cardiovascular disease, and diabetes,” Cao told Discover Magazine.
While more research is needed, use of the UK’s Biobank of healthcare data—including clinical laboratory test results—enabled the WashU Medicine researchers to determine that accelerated aging among young adults is happening with some regularity. This shows that capabilities in computer analysis are gaining more refined capabilities and are able to tease out insights impossible to achieve with earlier generations of analytical software.
These findings should inspire clinical laboratory professionals and pathologists to look for opportunities to collaborate in healthcare big data projects involving their patients and the communities they serve.
Researchers determined that as many as nine successive capillary blood drops must be collected and tested to achieve results that would be comparable to testing with venous blood
A new study is raising questions about the implications of using fingerprick blood samples for point-of-care tests. Done by researchers at Rice University’s Department of Bioengineering, the study suggests clinicians use measurements with caution when assessing patients’ conditions based on the results of clinical laboratory tests using a single drop of capillary blood collected by fingerstick.
Pathologists and clinical laboratory scientists were quick to call attention to the study, based on the press release Rice University issued. That’s because, for almost 30 years, medical laboratories have struggled to correlate the results for such biomarkers as glucose. It is common for capillary blood specimen collected by finger stick and tested on a point-of-care device to produce different results for the same patient when compared with that of a venous specimen tested on the automated, high-volume analyzes in a central laboratory. The Rice researchers offer useful insights about such variation. (more…)