Trigger found for autoimmune heart attacks

March 23, 2011, Joslin Diabetes Center

People with type 1 diabetes, whose insulin-producing cells have been destroyed by the body's own immune system, are particularly vulnerable to a form of inflammatory heart disease (myocarditis) caused by a different autoimmune reaction. Scientists at Joslin Diabetes Center have revealed the exact target of this other onslaught, taking a large step toward potential diagnostic and therapeutic tools for the heart condition.

Researchers in the lab of Myra Lipes, M.D., have shown in both mice and people that myocarditis can be triggered by a protein called alpha-myosin heavy chain, which is found only in heart muscle and in especially low quantities in human heart tissue.

While myocarditis often follows viral attacks or other infections, Dr. Lipes and her colleagues previously demonstrated that mice genetically modified to model type 1 diabetes could generate myocarditis spontaneously.

In their latest work, reported online in the , the scientists analyzed blood from such mice and identified two types of autoimmune response directed specifically against the protein, with the first response directed by a specialized kind of called T cells and the second by antibodies.

In both mice and people, T cells are "trained" by specialized cells in the thymus, a small organ in front of the heart, to recognize the body's own cells and refrain from attacking them. The researchers found, however, that in mice these specialized training cells couldn't train on the alpha-myosin heavy chain protein because none of that protein was being produced in those cells.

Next, the scientists showed that the disease didn't develop in similar mice that were genetically engineered to produce the protein in the specialized training cells. "You can totally protect those mice from mortality, which is really extraordinary," says Dr. Lipes, an Investigator in Joslin's Section on Islet Cell & Regenerative Biology and an Assistant Professor at Harvard Medical School.

Furthermore, the studies also indicated that alpha-myosin heavy chain was not present in human thymus and that the that sought out the protein could be found in the blood of healthy people. In patients with myocarditis, levels of these cells soared.

The investigation, Dr. Lipes says, suggests that people who are otherwise vulnerable to autoimmune conditions, such as those with , may be particularly vulnerable to this risk to their hearts.

Myosin heavy chain proteins are found in two very similar forms in human hearts: alpha-myosin heavy chain, which supports fast muscle contraction and may be particularly prevalent in athlete's hearts, and beta-myosin heavy chain, which is much more common and functions in slower muscle contraction. "We're trying to figure ways to identify the fragment of alpha-myosin heavy chain that is different, because that could aid in developing diagnostic tools and therapies," says Dr. Lipes.

More information: www.jci.org/articles/view/4458 … ca730049533908ae28b8

Related Stories

Recommended for you

Anemia discovery offers new targets to treat fatigue in millions

January 22, 2018
A new discovery from the University of Virginia School of Medicine has revealed an unknown clockwork mechanism within the body that controls the creation of oxygen-carrying red blood cells. The finding sheds light on iron-restricted ...

More surprises about blood development—and a possible lead for making lymphocytes

January 22, 2018
Hematopoietic stem cells (HSCs) have long been regarded as the granddaddy of all blood cells. After we are born, these multipotent cells give rise to all our cell lineages: lymphoid, myeloid and erythroid cells. Hematologists ...

How metal scaffolds enhance the bone healing process

January 22, 2018
A new study shows how mechanically optimized constructs known as titanium-mesh scaffolds can optimize bone regeneration. The induction of bone regeneration is of importance when treating large bone defects. As demonstrated ...

Researchers illustrate how muscle growth inhibitor is activated, could aid in treating ALS

January 19, 2018
Researchers at the University of Cincinnati (UC) College of Medicine are part of an international team that has identified how the inactive or latent form of GDF8, a signaling protein also known as myostatin responsible for ...

Bioengineered soft microfibers improve T-cell production

January 18, 2018
T cells play a key role in the body's immune response against pathogens. As a new class of therapeutic approaches, T cells are being harnessed to fight cancer, promising more precise, longer-lasting mitigation than traditional, ...

Weight flux alters molecular profile, study finds

January 17, 2018
The human body undergoes dramatic changes during even short periods of weight gain and loss, according to a study led by researchers at the Stanford University School of Medicine.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.