November 1, 20141

Autoimmune Alert:

The Rise of Autoimmune Diseases

How and why the body attacks itself and what we

can begin to do about it

Lisa Christopher-Stine, MD, MPH

Associate Professor of Medicine and Neurology

Director, Johns Hopkins Myositis Center

The Johns Hopkins University School of Medicine

Division of Rheumatology

Department of Medicine

Disclosures

• Intellectual property rights regarding an

autoimmune statin-associated

myopathy assay (Inova Diagnostics)

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Our Agenda Today

• Science class: What is autoimmunity

anyway?

• Examples of common (and uncommon)

autoimmune diseases

• Why are these diseases are on the rise?

• New pathways of diagnosis: understanding

the interplay of genes and the environment

• Treatment and Prevention

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What is autoimmunity anyway?

Auto = self

Immunity = the state of having sufficient biological

defenses to avoid infection, disease, or other unwanted

biological invasion. (The failure of an organism to

recognize its own constituent parts as self, thus leading

to an immune response against its own cells and

tissues.)

Any disease that results from such an aberrant immune

response is termed an autoimmune disease.

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Examples of Some Autoimmune Diseases

• Celiac Disease

• Crohn’s Disease

• Type 1 Diabetes

• Sarcoidosis

• Systemic lupus erythematosus (SLE)

• Sjögren's syndrome

• Hashimoto's thyroiditis and Graves' disease

• Rheumatoid arthritis (RA)

• Dermatomyositis (DM)

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Type 1 Diabetes

• Type 1 diabetes occurs when the body's own

immune system destroys the insulin-producing cells

of the pancreas.

• Between 2001 and 2009, the incidence of type 1

diabetes increased by 23%, according to The

American Diabetes Association.

• Finland showed a similar increase.

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Celiac Disease

• The incidence of celiac disease, which

causes the body's immune system to attack

the small intestine, is also on the rise,

according to the U.S. National Institutes of

Health and the University of Chicago Celiac

Disease Center.

• In the United States, 1 in 133 people are

affected by celiac disease.

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Immunology 101

Antigen: In immunology, an antigen is a substance foreign to the

body which, once in the body, attracts and is bound to a respective

and specific antibody.

Antibody: An antibody is a protein produced by the body's immune

system when it detects harmful substances (the antigens)

Autoantigen- usually a normal protein or complex of proteins (and

sometimes DNA or RNA) with in your body that is inappropriately

recognized by the immune system as foreign)

Autoantibody– a protein manufactured by the immune system that

is directed against one or more of the individual's own proteins

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Evolution of understanding how

our immune system sees “self”

• Horror autotoxicus (Paul Ehrlich)

-wherein a "normal" body does not

mount an immune response against its

own tissues (autoimmunity is abnormal)

Immunological tolerance to self-antigens

(Noel Rose) (autoimmunity is normal)

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• Autoimmune diseases are not even

widely taught in medical school until the

late1970s and 1980s.

• We are waging a “war on cancer” for a

long time by that point, yet autoimmune

diseases are barely making it to the

radar – just 30 years ago!

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Epidemiology

• Over 100 autoimmune diseases

• Women are, on average, 3x more likely to get an autoimmune

disease than a man (For lupus, 9:1)

• 1 in 12 people – 24 million Americans or more- and 1 in 9

women have an autoimmune disease.

• Despite the wide prevalence 9 out of 10 Americans could not

name a single autoimmune disease when prompted to do so.

• Over the past 30 years rates of many of these diseases are

doubling and tripling

• Often missed by providers; Mental health professionals were

often the first to make a correct diagnosis

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Autoimmune Diseases: Organ

(and Doctor!) specific or systemic

• Rheumatoid arthritis (RHEUMATOLOGIST)

• Type 1 Diabetes (ENDOCRINOLOGIST)

• M.S (NEUROLOGIST)

• Celiac sprue (GASTROENTEROLOGIST)

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What causes these diseases?

• Nobody knows for sure – most of the

time

• Cancer?

• Estrogen – exogenous/endogenous?

• Genetic Predisposition

• Diet?

• Environment (toxins, medication, and

food)

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Cancer

• Recent work published in Science has elucidated the

long-known connection between cancer and

autoimmunity.

• Some cancers have the ability to mutate self-proteins

and make them foreign to one’s own immune system,

thus prompting the body to attack itself.

• While this can create an important and helpful anti-

tumor response, the cross reactivity against other

proteins begins an all-out attack on all other healthy

tissues as well.

Science. 2014 Jan 10;343(6167):152-7 14

Estrogen

• Common sense would lead us to believe that if autoimmunity

preferentially affects women, then surely the sex hormones

should be an important determinant of autoimmune disease.

• Not shown to be conclusive –contraceptives in SLE (lupus)

• In fact, in 2004, the Safety of Estrogen in Lupus Erythematosus-

National Assessment (or the SELENA trial) found that birth

control pills do not increase flares in patients with lupus

N Engl J Med. 2005 Dec 15;353(24):2550-815

We are what we eat:

What about salt? Yes- salt!

• A recent study demonstrated a surprising connection between salt and autoimmunity: salt influences

susceptibility to autoimmune diseases ( multiple sclerosis, rheumatoid arthritis and inflammatory bowel

disease).

• The research team found that they could induce more severe forms of autoimmune diseases, and at higher

rates, in mice fed a high-salt diet than in those that were fed a normal diet.

• High-salt diet alone did not cause autoimmune diseases. Genetic predisposition plays a role too.

• Th17 immune cells are known to induce autoimmune diseases (like psoriasis). Researchers explored what

the right activity levels of these cells should be when it comes to promoting a healthy immune system-too

little activity leaves a person susceptible to infections; too much activity can lead to autoimmune diseases.

• They took 18 different “snapshots” of developing Th17 cells, to see what was happening inside them as

they developed. Then, one-by-one, they silenced, or ‘switched off,' the genes responsible for making these

cells, to see what would happen.

• To test its role in autoimmune disease, they examined a mouse disease known as experimental

autoimmune encephalomyelitis (EAE) that closely mimics multiple sclerosis in humans.

• Wen one particular gene, called serum glucocorticoid kinase 1 (SGK1), was turned off in mice, Th17 cells

were not produced. That specific gene had previously been found in gut and kidney cells, where it plays a

role in salt absorption.

• Mice lacking the SGK1 protein had less severe symptoms and significantly reduced rates of the disease,

• When the researchers further explored this observation by feeding mice a high-salt diet, the presence of the

SGK1 gene in immune cells caused an increase in the amount of Th17 cells, leading to autoimmune

disease.

Kuchroo, V. Sciencehttp://www.brighamandwomens.org/about_bwh/publicaffairs/news/publications/DisplayBulletin.aspx?articleid=5901

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“Genetics loads the gun but

the environment pulls the

trigger.”

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Environment vs. Genes

Twin disconcordance

30% concordance rate amongst

monozygotic twins

Statins as a model of autoimmune

disease trigger

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"With the rapid increase in autoimmune diseases, it clearly

suggests that environmental factors are at play due to the

significant increase in these diseases. Genes do not change in

such a short period of time.“

-Virginia T. Ladd, President and Executive Director of the

American Autoimmune Related Diseases Association (AARDA)

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Our environment…in utero

• In a study spearheaded by the Environmental Working Group (EWG),

researchers at two major laboratories found an average of 200 industrial

compounds, pollutants, and other chemicals in 10 newborn babies, with a total

of 287 chemicals found in the group.

• A broad array of pollutants collectively known to present potential risks to nearly

every organ and system in the body were found in the umbilical cord blood of

these 10 babies: pesticides, consumer product ingredients, and wastes from

burning coal, gasoline, and garbage. .

• Of the 287 chemicals found in newborn umbilical cord blood, 180 cause cancer

in humans or animals, 217 are toxic to the brain and nervous system, and 208

cause developmental problems. 101 chemicals found in all cord blood tested.

http://www.ewg.org/node/18504/related/clip 20

But what can we do to try to

protect ourselves?

• Chronic stress

• e.g., cytokines are found in spinal cord in MS

– but also found in higher levels in people

who go through chronic stress.

• Diet (GMOs? Gluten?)

• Smoking

• Seek a physician who will listen.

• Consider using Green cleaning products.

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What do we need to do as we look

to the future?

• Better data documenting the frequency

and location of autoimmune diseases in

the population: “a national registry”

• NIH dollars allocated toward

autoimmune disease research

• “Autogen” joins carcinogen in our

lexicon

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Take Home Messages

• Autoimmunity is rising – not explained by better

diagnosis/recognition alone

• Over 100 autoimmune diseases and most Americans cannot

name one

• 1 in 12 Americans affected by autoimmune disease

• Causes of autoimmunity and its increase remain unknown but

genetics and environment likely play a role

• Modifiable risk factors may include diet (GMO? gluten? salt?),

habits (smoking), chemical burden reduction (cleaning products,

make-up)

• Demand research funding from NIH and other government and

private sources

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• Autoimmune Diseases : “The next

Inconvenient Truth--The Global

Warming of Women’s Health”

– Donna Nakazawa , The Autoimmune Epidemic

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Thank you!