Accidental lab results could mean new anemia treatment


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Anemia is the commonest blood disorder in the U.S. Those who live with too few red blood cells battle fatigue, weakness, shortness of breath and cognitive problems. But surprising news comes from the University of Virginia (UVA). The unexpected outcome of an ordinary lab experiment at the School of Medicine there has resulted in researchers discovering a new way to generate the production of red blood cells.


Feeling flat


Around 3.5 million people have anemia in the U.S, and it's women, young children, the elderly and those with chronic diseases who suffer most. Anemics have a shortage of the red blood cells that contain the hemoglobin needed to transport oxygen around the body. This means they can regularly lack energy and feel fatigued. There are many causes for the condition including iron deficiency and vitamin deficiencies as well as bigger problems such as kidney disease and cancer.

However, it wasn't anemia that the researchers at UVA were investigating when they made their curious discovery. Dr. Thomas J. Braciale and his team members were actually observing the role of dendritic cells in the lungs. These cells are part of the body's immune system and have been traditionally thought to be sensors of infection and inflammation — helping the body combat the antigens that trigger an immune response. But a lab test at UVA involving the flu virus produced a completely unforeseen effect in mice that ultimately revealed an entirely new aspect to the cells' function.


An unknown quantity


To examine the action of dendritic cells, the researchers had been injecting mice with the flu virus and a certain antibody that blocks a particular molecule. The unexpected effect of this was that the spleens of the mice enlarged massively. Surprised, the scientists repeated the experiment — and got the same results. "We did it again and I didn't believe it," Braciale recalls. Curious to know whether the results were reliant on both or only one of the injections, they tried again with just the antibody. The same results came back again. "After much consultation," says Braciale, "we decided we were inducing stress erythropoiesis."

Stress erythropoiesis occurs when the body produces more red blood cells as a result of injury or other stress. Braciale realized they had accidentally found a "switch" that could be flipped to prompt red blood cell production. "In [a] very basic way," he says, "what we've discovered is that the process of regulating stress in the body is mediated…by these dendritic cells." Though it is known that stress erythropoiesis is caused by disease, the experiment shows the existence of other causes. "Stress can be a variety of different stresses," says Braciale. "It doesn't have to be infection; it doesn't have to be inflammation. It can be anemia. It can be hemorrhage."


Rehumanize yourself


Though a great deal more investigation needs to be carried out until the work can progress to human trials, Braciale and his team are optimistic. "We're very excited to see where this goes. We know that the same things can be done in humans in the following sense. There are mice called humanized mice. These are mice that are engineered so they have a human blood system. And if you inject these mice with this antibody, they'll make red blood cells."

The results, though greatly encouraging were, he says, entirely unexpected: "These cells act to initiate this response that, until this report, there's been really no evidence that these [dendritic] cells ever participate in making red blood cells." The work by Braciale and his colleagues is published in the Journal of Clinical Investigation.


A war on disease


WebMD notes that more than 400 different types of anemia have been identified. Generally, these fall into one of three groups: anemia caused by blood loss, by decreased or faulty red blood cell production or by destruction of the red blood cells themselves. Contributory factors can include a diet lacking in certain nutrients (iron, vitamin B-12 and folic acid are the main culprits), intestinal disorders, menstruation and pregnancy as well as chronic conditions like cancer, kidney and liver failure or ulcers. Those who have a family history of the diseases like sickle-cell anemia are also at risk.

The team's findings could mean a significant step forward in the battle against the condition — allowing doctors to turn on red blood cell production whenever necessary could result in serious benefits for people with diabetes, kidney disease or cancer, and for older people for whom anemia can become a chronic problem. It's also feasible, researchers say, that the trigger could be used in situations where traditional methods of blood transfusion aren't always possible — to treat people who cannot receive transfusions because of religious beliefs, for example, or on the battlefield to help wounded soldiers until they can receive full medical treatment.