Autoimmune Diseases Result of Mutations & Infection, Study Suggests

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Autoimmune Diseases Result of Mutations and Infection, Study Suggests

Dec 19 2000 16:07:28

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PHILADELPHIA -- Scientists who study the immune system say they've taken

a big step toward understanding why your body's defensive cells

sometimes turn against you. Chance mutations, coupled with a viral

infection, can trigger autoimmune reactions that create a potentially

deadly family feud within your body.

The finding, which appears in the current issue of the Journal of

Experimental Medicine, is preliminary and unlikely to produce any help

for patients in the near future. However, researchers say, it could one

day lead to treatments for lupus, rheumatoid arthritis and early-onset,

or Type I, diabetes. Together, autoimmune diseases are among the top 10

killers of women in America.

The notion that infections may be at the root of autoimmune disorders

has been around for a century, says Dr. Noel Rose, a specialist in the

disorders at s Hopkins University. " It's really very plausible, but

when you get down to it there's really not much evidence that it truly

occurs, " says Rose, who is also chairman of the scientific advisory

panel of the American Autoimmune Related Diseases Association.

A prime example of the link is rheumatic heart disease, an autoimmune

attack on heart tissue that's thought to result from repeated strep

infections during childhood.

The latest study offers at least one explanation of how your immune

system can turn into your worst enemy. The research, led by

Caton, of the Wistar Institute in Philadelphia, hinges on a class of

immune agents called memory B cells. They are the first dominoes in the

cascade of reactions that make up an immune response, and they have two

key jobs.

The first is to recognize an invading organism, such as a virus, and

warn other immune cells of its presence. They do this by generating

proteins, called antibodies, which are specific to the microbe. They can

also neutralize the invader by attaching themselves to it. B cells " help

keep you from dying " within days from the initial infection, says Caton.

But there's a subset of B cells that, when they meet an invader, don't

do anything immediately. Instead, they retreat to the spleen, and with

the help of other immune cells, they begin to mutate randomly and with

remarkable haste, he explains.

In clusters known as germinal centers, they refine themselves into

highly specific cells that flood the bloodstream and defeat the

infection. This process, which occurs about a week after initial

infection, also gives the body a " memory " of the invader, Caton says.

That helps them fight off subsequent attacks from the same organism.

It's also the reason vaccines work, since these B cells live a long time

and " do a better job of recognizing the virus than the ones you have

inherited, " he says.

In the latest study, Caton and his colleagues showed that, during their

time in the spleen, these B cells can mutate and become hostile to your

body. Using a strain of mice genetically modified to express an

influenza protein, hemagglutinin, they were able to disguise the viral

protein as part of the body.

The modified mice appeared to be healthy. But when they infected the

animals with flu, their immune cells launched a muted attack against the

transferred protein.

Since B cells in the first wave of attack die off, the autoimmune

reaction had to originate with the B cells produced in the second phase,

Caton says. In other words, the combination of random mutations with a

viral invasion sparked an autoimmune response, albeit a mild one, he

says.

What's not clear is why autoimmune reactions choose to pick on

particular tissues, like the joints in arthritis or pancreas in

diabetes. " What makes it harmful rather than benign is similar to

saying, 'Why are

some cell masses benign and others malignant?' " Caton says. " How that

decision is made is a big mystery. "

If infections do indeed spark autoimmune reactions, then vaccination

would be the obvious answer. Yet Rose says at least one other new study

seems to show the incidence of autoimmune disease rises with more

immunization. " That makes life very interesting for people who study

these illnesses, " he says.

SOURCES: Interviews with J. Caton, Ph.D., associate professor,

Wistar Institute, Philadelphia; Noel R. Rose, M.D., Ph.D., professor of

pathology and immunology, s Hopkins University, Baltimore; Dec. 18,

2000 Journal of Experimental Medicine.