Tag: blood donation

Research Identifies Beneficial Genetic Changes in Regular Blood Donors

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Researchers at the Francis Crick Institute have identified genetic changes in blood stem cells from frequent blood donors that support the production of new, non-cancerous cells.

Understanding the differences in the mutations that accumulate in our blood stem cells as we age is important to understand how and why blood cancers develop and hopefully how to intervene before the onset of clinical symptoms.

As we age, stem cells in the bone marrow naturally accumulate mutations and with this, we see the emergence of clones, which are groups of blood cells that have a slightly different genetic makeup. Sometimes, specific clones can lead to blood cancers like leukaemia.

When people donate blood, stem cells in the bone marrow make new blood cells to replace the lost blood and this stress drives the selection of certain clones.

Blood donation impacts makeup of cell populations

In research published in Blood, the team at the Crick, in collaboration with scientists from the DKFZ in Heidelberg and the German Red Cross Blood Donation Centre, analysed blood samples taken from over 200 frequent donors – (three donations a year over 40 years, more than 120 times in total) – and sporadic control donors who had donated blood less than five times in total.

Samples from both groups showed a similar level of clonal diversity, but the makeup of the blood cell populations was different.

For example, both sample groups contained clones with changes to a gene called DNMT3A, which is known to be mutated in people who develop leukaemia. Interestingly, the changes to this gene observed in frequent donors were not in the areas known to be preleukaemic.

A balancing act

To understand this better, the Crick researchers edited DNMT3A in human stem cells in the lab. They induced the genetic changes associated with leukaemia and also the non-preleukaemic changes observed in the frequent donor group.

They grew these cells in two environments: one containing erythropoietin (EPO), a hormone that stimulates red blood cell production which is increased after each blood donation, and another containing inflammatory chemicals to replicate an infection.

The cells with the mutations commonly seen in frequent donors responded and grew in the environment containing EPO and failed to grow in the inflammatory environment. The opposite was seen in the cells with mutations known to be preleukaemic.

This suggests that the DNMT3A mutations observed in the frequent donors are mainly responding to the physiological blood loss associated with blood donation.

Finally, the team transplanted the human stem cells carrying the two types of mutations into mice. Some of these mice had blood removed and then were given EPO injections to mimic the stress associated with blood donation.

The cells with the frequent donor mutations grew normally in control conditions and promoted red blood cell production under stress, without cells becoming cancerous. In sharp contrast, the preleukaemic mutations drove a pronounced increase in white blood cells in both control or stress conditions.

The researchers believe that regular blood donation is one type of activity that selects for mutations that allow cells to respond well to blood loss, but does not select the preleukaemic mutations associated with blood cancer.

Interactions of genes and the environment

Dominique Bonnet, Group Leader of the Haematopoietic Stem Cell Laboratory at the Crick, and senior author, said: “Our work is a fascinating example of how our genes interact with the environment and as we age. Activities that put low levels of stress on blood cell production allow our blood stem cells to renew and we think this favours mutations that further promote stem cell growth rather than disease.

“Our sample size is quite modest, so we can’t say that blood donation definitely decreases the incidence of pre-leukaemic mutations and we will need to look at these results in much larger numbers of people. It might be that people who donate blood are more likely to be healthy if they’re eligible, and this is also reflected in their blood cell clones. But the insight it has given us into different populations of mutations and their effects is fascinating.”

Hector Huerga Encabo, postdoctoral fellow in the Haematopoietic Stem Cell Laboratory at the Crick, and first joint author with Darja Karpova from the DKFZ in Heidelberg, said: “We know more about preleukaemic mutations because we can see them when people are diagnosed with blood cancer.

“We had to look at a very specific group of people to spot subtle genetic differences which might actually be beneficial in the long-term. We’re now aiming to work out how these different types of mutations play a role in developing leukaemia or not, and whether they can be targeted therapeutically.”

Source: The Francis Crick Institute

Gut Bacteria Enzymes to Turn Donated A and B Blood Universal

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The quest to develop universal donor blood has taken a decisive step forward. Researchers in Denmark have discovered enzymes that, when mixed with red blood cells, are able to remove specific sugars that make up the A and B antigens in the human AB0 blood groups. The results appear in Nature Microbiology.

“For the first time, the new enzyme cocktails not only remove the well-described A and B antigens, but also extended variants previously not recognised as problematic for transfusion safety. We are close to being able to produce universal blood from group B donors, while there is still work to be done to convert the more complex group A blood. Our focus is now to investigate in detail if there are additional obstacles and how we can improve our enzymes to reach the ultimate goal of universal blood production,” says Professor Maher Abou Hachem, who is the study leader at Technical University Denmark (DTU) and one of the senior scientists behind the discovery.

He states that the discovery is the result of combining the expertise of DTU researchers in enzymes from the human gut microbiota and Lund University researchers in carbohydrate-based blood groups and transfusion medicine.

High demand for donor blood

Human red blood cells carry specific complex sugars structures (antigens) that define the four AB0 blood groups A, B, AB and 0. These antigens control compatibility between donors and recipients for safe blood transfusion and organ transplantation. Donor blood is screened for disease markers and the main blood groups. It can then be stored refrigerated for up to 42 days.

The need for donor blood is high due to the elderly making up a larger proportion of the population and more patients undergoing blood-intensive medical procedures. Successfully converting A or B blood types into AB0 universal donor blood can markedly reduce the logistics and costs currently associated with storing four different blood types. In addition, the development of universal donor blood will lead to an increased supply of donor blood by reducing the waste of blood approaching its expiry date.

The reason why it is necessary to remove the A and B antigens to create universal donor blood is because they can trigger life-threatening immune reactions when transfused into non-matched recipients.

The concept of using enzymes to generate universal donor blood was introduced more than 40 years ago. Since then, higher efficiency enzymes to remove the A and B antigens were discovered, but researchers are still not able to explain or abolish all immune reactions related to the blood, and therefore these enzymes are still not used in clinical practice.

Enzymes from the gut

The research groups from DTU and Lund University have gone new ways to find enzymes that can remove both the A and B blood antigens and the sugars that block them. The research teams discovered new mixtures of enzymes from the human gut bacterium Akkermansia muciniphila that feeds by breaking down the mucus, which covers the surface of the gut. It turns out that these enzymes are exceptionally efficient, as the complex sugars at the surface of the intestinal mucosa share chemical resemblance with those found at the surface of blood cells.

“What is special about the mucosa is that bacteria, which are able to live on this material, often have tailor-made enzymes to break down mucosal sugar structures, which include blood group AB0 antigens. This hypothesis turned out to be correct,” says Maher Abou Hachem.

The researchers in this study tested 24 enzymes, which they used to process hundreds of blood samples.

“Universal blood will create a more efficient utilisation of donor blood, and also avoid giving AB0-mismatched transfusions by mistake, which can otherwise lead to potentially fatal consequences in the recipient. When we can create AB0-universal donor blood, we will simplify the logistics of transporting and administering safe blood products, while at the same time minimizing blood waste” says Professor Martin L. Olsson, the leader of the study at Lund University.

The researchers from DTU and Lund University have applied for a patent on the new enzymes and the method for enzyme treatment and expect to make further progress on this in their new joint project over the next three and a half years. If successful, the concept needs to be tested in controlled patient trials before this can be considered for commercial production and clinical use.

The initial research project is funded by the Independent Research Fund Denmark (Technology and Production Sciences, FTP), the Swedish Research Council, ALF grants from the Swedish government and county councils as well as the Knut and Alice Wallenberg Foundation and Research Fund Denmark, Natural Sciences, FNU), while the new continued project is funded by the Novo Nordisk Foundation, Interdisciplinary Synergy Programme.

The AB0 blood group antigens found on the surface of red blood cells are also found on the mucosal layer that lines the surface of the gut. Researchers have harnessed a specialised human gut bacterium and its ability to use these antigens as nutrients to discover and develop two enzyme mixtures that convert group A and B red blood cells into universal donor blood. Graphic: Mathias Jensen, postdoc at DTU.

About Akkermansia muciniphila

Akkermansia muciniphila is a bacterium found abundantly in the guts of most healthy humans. This bacterium can break down mucus in the gut and produces beneficial compounds such as the short-chain fatty acid propionate, in addition to exerting beneficial effects on body weight and metabolic markers.

Source: Technical University of Denmark

An Estimated 70% of South Africans Have Had COVID

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Writing for GroundUpDr Alex Welte unpacks the results of the latest blood donor survey, which suggests that some 70% of South Africans have had a COVID infection.

The South African National Blood Service (which handles the blood supply for eight provinces) and the Western Cape Blood Service have been testing some donors for Covid antibodies over the last year or so. This has contributed to our understanding of how many people have been infected by SARS-CoV-2 (the virus that causes Covid), and what proportion of infections lead to death. It may help us plan for future waves, though exactly how is complicated.

On the assumption that another wave towards the end of 2021 was nearly inevitable – but before we all heard about omicron – it was decided to perform more such testing in early November. The numbers are now out.

The headline results are:

  • Overall about 80% of black donors had previously had Covid, and 40% of white donors.
  • There is no meaningful variation between age groups and sexes.
  • This latest survey did not include Western Cape data.
  • The test used does not detect the antibodies produced in response to vaccination, so this really is an estimate of people who have been infected.

While blood donors are not perfectly representative of the country’s population, we can take into account differences between the racial breakdown of the donor population and the racial breakdown of the general population. This means that our face-value national estimate is that about 70% of people had been infected before the omicron wave hit.

Since then we’ve had the omicron wave. We would very much like to know how many people are infected now, but there’s really no simple way to derive this number. Researchers are now updating their models with this additional piece of data, and we may see some estimates soon.

With that caution, here is my back-of-the-envelope estimate:

  • Omicron seems to have little trouble infecting people who have been infected by other variants, though there is some protection from prior infection and vaccination.
  • By late last year, quite a bit more than half the population had already had a prior infection.
  • Hence, I estimate that about half of the omicron wave infections were in previously uninfected individuals.
  • Given the infection detection rate estimates from previous waves, and a number of plausible sources of possible variation in this rate, I estimate the detection rate at about 1 in 10.
  • Given the roughly 700 000 cases reported between mid November and mid February, we get an estimate of 7 million cases, and therefore 3.5 million new infections.
  • Given our population of about 60 million, this is roughly an additional 6%.
  • Bottom line: it’s not crazy to estimate that about three-quarters of South Africans have by now been infected. But I would not be surprised if serious models come up with even higher estimates.

A troubling result of the survey is that once more it shows the serious racial disparities in South Africa. I don’t know if this carried over to the omicron wave. Estimating the racial breakdown of infection after omicron depends in a complicated way on variations in housing, lifestyle, access to vaccination, and all the usual factors that shape daily life in our country.

Dr Welte helped design and implement the blood donor survey.

Source: GroundUp