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Researchers Gain Better Understanding Of Deadly Autoimmune Heart Ailment That Affects Young Adults

Date:
July 31, 2001
Source:
Johns Hopkins University Bloomberg School Of Public Health
Summary:
Researchers at the Johns Hopkins Bloomberg School of Public Health have discovered that complement, a key protein of the innate immune system, is critical to the development of autoimmune myocarditis. According to the study appearing in the August 2001 issue of Nature Immunology, the researchers prevented autoimmune myocarditis in mice by blocking the production of complement and by blocking its interaction with two key complement receptors.

Researchers at the Johns Hopkins Bloomberg School of Public Health have discovered that complement, a key protein of the innate immune system, is critical to the development of autoimmune myocarditis. According to the study appearing in the August 2001 issue of Nature Immunology, the researchers prevented autoimmune myocarditis in mice by blocking the production of complement and by blocking its interaction with two key complement receptors. The study examines the role of the innate immune system during the formation of autoimmune myocarditis, which may lead to better diagnosis and prevention of this deadly disease and other autoimmune disorders.

Myocarditis is an inflammation of the heart muscle and is a principal cause of heart disease and sudden cardiac death in young adults. It is often caused by infection from a coxsackie virus. While most people recover from viral myocarditis with no ill effects, a small number of people develop autoimmune myocarditis in which the body’s own immune system attacks the heart muscle, eventually leading to heart failure.

“We wanted to know why myocarditis triggers an autoimmune response in a small group of people. Our research shows that complement and its receptors are key pieces of that puzzle,” says Noel R. Rose, MD, PhD, professor molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health and professor of pathology and medicine at the Johns Hopkins School of Medicine.

As Dr. Rose explains, the body has two levels of defense in the immune system: the innate immune response, which we are born with, and the adaptive immune response, which we learn by experience. The innate immune system "holds the fort" with complement, which motivates T-cells and cytokines of the adaptive immune system to mount a response and fight off the infection. It is during this learning phase, the researchers believe, that complement plays a critical role in the development of autoimmune myocarditis.

For the study, Dr. Rose and his colleagues examined mice infected with a coxsackie virus that causes myocarditis. Some of mice were given snake venom to deplete complement. None of the mice depleted of complement developed any signs of myocarditis, while four out of six control mice developed the disease.

During the experiments, the researchers also determined that two cell receptors, CR-1 and CR-2, bind with complement to modulate T-cell activation. The researchers devised another experiment to block complement receptors in the mice. Only one mouse out of eight with blocked complement receptors showed signs of mild myocarditis, while the control mice, without blocked receptors, developed severe autoimmune myocarditis.

"This finding may aid the development of novel therapeutic approaches for the treatment of human autoimmune diseases such as diabetes, multiple sclerosis, and myocarditis. More research is needed to investigate the role of complement receptors in T-cell activation and cytokine production," adds Dr. Rose.

###

Ziya Kaya, Marina Afanasyeva, Yan Wang, K. Malte Dohmen, Jens Schlichting, Theresa Tretter, DeLisa Fairweather, and V. Michael Holers contributed to the research of the this study.

Funding for the study was provided by the National Institutes of Health, Deutsche Herzstiftung and Deutsche Forschungsgemeinscharft.


Story Source:

The above story is based on materials provided by Johns Hopkins University Bloomberg School Of Public Health. Note: Materials may be edited for content and length.


Cite This Page:

Johns Hopkins University Bloomberg School Of Public Health. "Researchers Gain Better Understanding Of Deadly Autoimmune Heart Ailment That Affects Young Adults." ScienceDaily. ScienceDaily, 31 July 2001. <www.sciencedaily.com/releases/2001/07/010730081504.htm>.
Johns Hopkins University Bloomberg School Of Public Health. (2001, July 31). Researchers Gain Better Understanding Of Deadly Autoimmune Heart Ailment That Affects Young Adults. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2001/07/010730081504.htm
Johns Hopkins University Bloomberg School Of Public Health. "Researchers Gain Better Understanding Of Deadly Autoimmune Heart Ailment That Affects Young Adults." ScienceDaily. www.sciencedaily.com/releases/2001/07/010730081504.htm (accessed July 31, 2014).

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