http://unisci.com/stories/20013/0730014.htm
30-Jul-2001
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.
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 of 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 it, 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 the 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,” Dr. Rose says.
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.
[Contact: Tim Parsons]
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.