Autoimmune diseases activated by environmental exposure

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Mysteries of autoimmune diseases unravel

Osborne, left, notes a lunchtime caloric intake for her

daughter Reagan , right, in their Westborough, Mass., home.

Reagan, 9, was diagnosed May 31 with Type 1 diabetes.

Enlarge image Enlarge By B. Plowman for USA TODAY

Osborne, left, notes a lunchtime caloric intake for her

daughter Reagan , right, in their Westborough, Mass., home.

Reagan, 9, was diagnosed May 31 with Type 1 diabetes.

Welsh's daughter, Kylynn, 17, has a rare autoimmune disease

that resulted in uncontrolled swelling so severe it closed her throat.

Enlarge By Todd Plitt, USA TODAY

Welsh's daughter, Kylynn, 17, has a rare autoimmune disease

that resulted in uncontrolled swelling so severe it closed her throat.

By Anita Manning, USA TODAY

Just three months ago, Reagan , 9, was dangerously sick with

extremely high levels of sugar in her blood. Today she's back on her

feet and enjoying her first days in fourth grade.

Last week, Kylynn Welsh, 18, was in critical condition on a ventilator

in a New Jersey hospital, unable to breathe on her own because of

swelling that closed her throat. On Sunday, she was released from the

hospital and will soon be starting college.

These young people have very different illnesses with one thing in

common: Their immune systems have gone awry.

Scientists say immune disorders, which range from common diseases such

as juvenile diabetes or lupus to some so unusual that many doctors

have never heard of them, are among the most mysterious of ailments,

genetically complex and so diverse that estimating their true

prevalence is a guessing game. But with major advances in genetics and

exponential growth of knowledge about the immune system, scientists

say important discoveries are tantalizingly within reach.

" The capacity to explore the human genome has reached the worker bee, "

says Harley of the Arthritis and Immunology Research Program at

the Oklahoma Medical Research Foundation in Oklahoma City. " It has

filtered down far enough that we now have the capacity to do

experiments we only dreamed of 10 years ago. "

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Medical research

Now, he says, " the whole range of human disease is going to be studied

using this approach and will produce new clues that will be utterly

transforming in our ability to manipulate the fundamental disease

process. "

Disorders of the immune system can be debilitating and expensive, and

are likely to be much more common than previously realized.

But just how many people have them is not known, because such diseases

are not tracked. The National Institutes of Health estimated in a 2005

report that 5% to 8% of Americans, up to 23.5 million, have one or

more autoimmune diseases, which occur when the immune system launches

an attack on healthy cells within its own body.

In the current issue of the Journal of Clinical Immunology,

researchers estimate, based on a random telephone survey, that another

group of immune disorders called primary immune deficiency diseases

may afflict as many as one in 1,200. In these diseases, caused by an

inborn genetic defect, the body can't mount an effective immune

response to infection.

" Almost every autoimmune disease, with the exception of rheumatoid

arthritis, seems to be going up, " says immunologist Noel Rose,

director of the s Hopkins Autoimmune Diseases Research Center. But

whether that's because of an increase in disease or better recognition

of cases is not certain.

Wonder of nature

The immune system is nature's built-in security force. When working

properly, it detects an incoming attack upon the body, whether by

viruses or other organisms, and mounts a protective response. When the

invader is vanquished, it calls off the troops. But when that system

malfunctions, the body's internal security force can lay down its arms

or even turn on itself.

In some cases, diagnosis is a slam-dunk because symptoms are hard to

miss. But for others, it's not so clear. Pain or fatigue is hard to

measure, and other symptoms, such as inflammation or weight loss, can

have many causes.

" When you have type 1 diabetes, there's a relatively clear boundary

between when you have it and when you don't, " says Josiah Wedgwood,

chairman of the Autoimmune Diseases Coordinating Committee at the

National Institutes of Health. " With most of the other autoimmune

diseases, there isn't a clear boundary like that. There's a problem

called an ascertainment bias: You identify the sickest patients

always, but like an iceberg, are you only looking at the surface? And

what's beneath? "

Often, patients go from doctor to doctor, desperate for a diagnosis.

" We know from surveys there's a really unacceptable time from onset of

symptoms to diagnosis of primary immune deficiency, as high as nine

years, " says pediatric immunologist Jordan Orange of the University of

Pennsylvania and Children's Hospital of Philadelphia.

'A car without a brake'

For Kylynn Welsh, it took more than 12 years.

The teenager is missing a blood protein needed to stop the immune

response. If she gets a cut or a bump or if she catches a cold, her

body's immune system swings into gear, sending white blood cells and

fluids to the affected area, causing inflammation and swelling. But

her body can't turn off the response. " It's like driving a car without

a brake pedal, " Wedgwood says.

As a child, Kylynn would have unexplained bouts of swelling, says her

mother, Welsh. After gym one day, her legs swelled painfully.

Sometimes her belly would puff up, causing agonizing pain.

" One time, her face was so distorted that her scalp swelled down over

her eyes and she couldn't open her eyes, " Welsh says.

After four hospitalizations and dozens of medical evaluations, doctors

pinpointed the disease as hereditary angioedema, a disorder that is

usually inherited but can result from a genetic mutation before birth.

No one in her family has had it, Welsh says. " I said, 'OK, now I know

what devil I'm playing with.' "

In her most recent hospitalization, Kylynn went to Medical

Center in Camden, N.J., about 20 minutes from her family's home in

Delanco, N.J., to have dental work done, which requires that she be

intubated and given plasma infusions because of her immune system

disease. But " her throat started to bother her the day we were coming

in for the procedure, and before we could get a (hospital) bracelet on

her arm, her throat closed, " her mother says.

It was a moment of panic. " She was dying in front of me, " Welsh says.

A critical-care doctor recognized the signs of distress and said, "

'Let's go, let's go,' " Welsh says. He inserted a fiber-optic scope

through Kylynn's nose and throat to see where the swelling was, so he

could insert a breathing tube.

A new life with diabetes

In May, Reagan , who turns 10 next Sunday, complained to her

mother about being frequently thirsty and needing to get up at night

to go to the bathroom. She was tired and grumpy and was losing weight.

" I was thinking those are classic diabetes symptoms, " says her mother,

Osborne of Westborough, Mass. But " I didn't know they were

symptoms that needed immediate attention. "

It wasn't until Reagan felt sick to her stomach after being out to

dinner that her symptoms became truly alarming. She drank juice before

bed and in the morning was " lethargic and very unfocused. " When she

was no better the next day, Osborne took her to the emergency room.

There, she was diagnosed with type 1 diabetes, a disease in which the

immune system destroys insulin-producing cells. Reagan was in a state

of diabetic ketoacidosis, a dangerous condition caused by extremely

high blood sugar. After 31/2 days in the hospital, she was able to go

home to begin life with diabetes. She takes four shots of insulin a

day and tests her blood sugar six times a day.

Immune system disorders often cluster in families and within an

individual, says Virginia Ladd, president of the American Autoimmune

Related Diseases Association. " Once you have one, you have others.

Some patients say if you live long enough, you can collect them. "

Strumph, chief medical officer of the Juvenile Diabetes Research

Foundation, agrees. People with type 1 diabetes are more likely to

have other autoimmune disorders, such as thyroid disease or celiac

disease, an intestinal disorder, he says. " The factors that make

people have type 1 diabetes, whatever they are, have implications for

other autoimmune diseases. "

Scientists believe autoimmune diseases are caused by a genetic

predisposition activated by some environmental exposure.

" We don't understand all the factors influencing the immune system,

but there has been an explosion in interest, " Strumph says.

Possibilities include exposure to new germs, a result of international

travel and commerce, a deficiency in vitamin D, an excess of

cleanliness that stunts immune system development, even obesity.

But he and others who specialize in immune disorders are optimistic.

The development of huge public databases about human genetics and

technologies that allow scientists to test thousands of samples in a

day will lead to new drugs tailored to a person's genetic makeup, new

ways to predict susceptibility to disease and possibly ways to prevent

them.

It may be a decade or more before " the discoveries being made today

are fully realized in patients, " says Harley of the Oklahoma Medical

Research Foundation. But the advances in research capability of the

past several years are like " the difference between horseback and a

Learjet, " he says. " That's the kind of transition we're undergoing at

the moment. The country should have an appreciation for this and

celebrate it. Life is extremely complicated, and the fact that we

understand any of it is a miracle. "

Posted 19h 56m ago