Unraveling the Mystery of Autoimmunity

[Guest guest]

Unraveling the Mystery of Autoimmunity

Published on: March 5, 2003 Editorial Review: October

15, 2004

Everybody wants to have a strong immune system. The

immune system is the body's own personal Department of

Defense, protecting its health and integrity from

invading armies of harmful viruses and bacteria. Its

specialized cells, called lymphocytes, normally do a

fine job of keeping illness at bay, but sometimes they

slip up, sending us home with the flu.

Even with all the smart weaponry at its command, the

immune system can sometimes go awry, attacking targets

inside the very body it was designed to protect. This

is the explanation behind over 80 suspected autoimmune

diseases, including psoriasis, rheumatoid arthritis,

multiple sclerosis and juvenile diabetes.

Noel Rose, MD, Professor in the Department of

Pathology at s Hopkins School of Medicine and

Director of the s Hopkins Center for Autoimmune

Disease Research, has spent the better part of his

distinguished career following the common thread that

weaves these diseases together. In the following

remarks, he shows how autoimmune diseases of the skin,

joints, nerves and pancreas are fundamentally linked.

What is autoimmunity?

Traditionally, the immune response has been

understood as the body's method of defending itself

against disease, which it does by identifying and

destroying foreign invading microorganisms. By

contrast, autoimmunity involves an immune response to

something within the body itself.

How does the immune system distinguish between what

belongs in our bodies and what doesn't?

The job of the immune system is to produce antibodies

against antigens which cause harm. In fact, our immune

systems accomplish that task very well. Not only do we

produce antibodies to newly emerging infectious agents

but also to molecules produced in the laboratory that

may be used in certain types of medications. So why

don't we normally produce antibodies to molecules in

our own bodies? The answer lies in the complex

mechanisms that govern self-recognition and

self-tolerance.

We all produce lymphocytes that are potentially

capable of recognizing and even attacking " self. "

Normally, these cells are either deleted very early or

they're held in check by regulatory controls. When

these safeguards fail us, so-called autoantibodies

develop. All of us have autoantibodies - antibodies in

our blood that react with something in our own bodies.

Are you saying that autoantibodies and autoimmunity

are normal?

Autoimmunity is mostly harmless. Some immunologists

even believe it may be helpful. Autoantibodies may

help to remove worn out or dead cells, but firm

evidence for this is not yet at hand. Clearly, though,

an autoimmune reaction can go too far, and that's

where the problem begins.

What is autoimmune disease?

The definition of an autoimmune disease is sometimes

very hard to pin down. There is no universal agreement

on which diseases are autoimmune and which are not

autoimmune. Autoimmunity may be present in the

disease, but may not be actually causing it.

What causes some people to develop autoimmune

diseases in the first place?

The tendency to develop an autoimmune disease has

roots in both genetics and the environment. Autoimmune

diseases are different from other genetically

determined diseases that we're more familiar with,

like sickle cell anemia, where there's a single gene

and either you have it or you don't. In autoimmune

disease, there's an accumulation of a number of

different genes that, when added together, give a

heightened probability that you will develop an

autoimmune disease. About a third of the risk of

developing an autoimmune disease is inherited. That

means the other 66% is environmental. Even if you

inherit a genetic predisposition, the autoimmune

disease will not occur unless there's an environmental

trigger.

What are some conditions that are now considered

autoimmune diseases?

Interestingly, back in the 1960s, many of us

suspected that Type 1 diabetes might be an autoimmune

disease, but we couldn't really find substantial

evidence to support our suspicions. Later, it emerged

that the autoimmune form of diabetes is the

insulin-dependent form, sometimes called juvenile

diabetes or Type 1, which affects about 10% of

patients with diabetes. So that was a major surprise.

According to the current view, psoriasis is now

considered an autoimmune disease involving an immune

response that results in lesions in the skin. For

example, they may have been exposed to an infection,

and the infecting organism may have had an antigen - a

substance that resembles a component of the skin.

Whether psoriasis is caused by an internal or external

stimulus, the upshot is that there is an immune

response to something in the skin.

Another example is rheumatoid arthritis, a very

common disease. Patients with rheumatoid arthritis

have autoantibodies. We still don't know for certain

whether the autoimmunity we see in the disease is

actually causing the disease. That having been said,

virtually all of us now accept rheumatoid arthritis as

an autoimmune disease. Still, there's a little

uncertainty in the back of our minds that there could

be a virus, or something else, that's causing the

disease, and that the autoimmunity is merely an

accompaniment.

Is it important to establish the ultimate cause of

rheumatoid arthritis in order to treat it effectively?

At present, the ultimate cause is not a matter of

overwhelming importance, because what we treat are its

symptoms. The kinds of drugs we use today block the

substances that are produced during an immune

response, substances that are actually causing the

pathology of the disease. These drugs work. It's not

relevant whether the immune response that we're

blocking is actually a true autoimmune response or

whether it's a response to a hypothetical virus that

we've never found.

Finding the actual cause of the autoimmune disease

will probably become more of an issue in the future

years. We hope to see a whole new generation of

treatments based on a more advanced understanding of

autoimmunity as an underlying disease process.

Once a patient has a full-blown autoimmune disease,

what are today's preferred methods of treatment?

In some cases, we can treat an autoimmune disease by

replacing a lost function. That's what we do when we

give insulin for diabetes or thyroid hormone for

Hashimoto's thyroiditis. When these symptomatic

remedies fail, however, we must turn to

immunosuppression in order to down-regulate the entire

immune system. Obviously, this approach is hazardous,

because it makes people susceptible to infection, plus

most immunosuppressant drugs have severe side effects.

They're a last resort. Most physicians give them with

great reluctance.

We would much prefer to have a more targeted type of

therapy - one that turns down the disease-inducing,

damaging autoimmune response without interfering with

general immune function. Some of the newer biologic

drugs are an improvement over traditional

immunosuppressants, since they focus on the

inflammatory consequences of the autoimmune reaction.

But they still may have adverse effects in heightening

susceptibility to certain types of infection.

How would you assess the pace of medical discovery in

the field of autoimmunity? Is substantial progress

being made?

We're getting closer and closer to the root cause of

autoimmune disease. My vision is that someday we'll

identify the substance that gets the harmful

autoimmune disease process going. The goal is to make

people unresponsive to their own excessive autoimmune

response. We need to learn a lot more about how to

identify these offending antigens in people and how to

make people immunologically unresponsive. The fact

that we can do it in animals shows that it's possible.

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