Introduction Autoimmune Disease by Dr. Kelly Cobb

By Dr. Kelly Cobb

INTRODUCTION TO AUTOIMMUNE DISORDERS

The immune system represents an interface between a constant ever-changing external environment and an internal system that is striving to maintain homeostasis and defend its boundaries from harmful foreign invaders

Primary roles of the immune system

• Identify potentially infectious or injurious substances

• Distinguish self antigens from non-self antigens

• Assess the potential level of threat posed by infectious, toxic or non-self adherents

• Mount an appropriate response

• Repair any damage that ensues

Immune System Dysfunction

“ The immune system has begun over-responding

to normal benign immunogens, whether environmental or endogenous”

WHY ???

To understand why tolerance breaks down in autoimmune disease, it is important to understand the process by which the immune system finds and attacks foreign antigens.

Macrophages

• First cell type to act as a sentinel to detect and report about what it finds in the environment around it.

• Macrophage means "big eater."

• Constantly eating up a little bit of whatever surrounds it, cutting the ingested proteins up into small pieces (the antigens mentioned above), and then displaying these pieces of protein on its surface.

T cells• Macrophage presents these antigens to the T cell• Primary decision maker in the immune process• Highly specialized• Each are different from every other one.• On their surface, T cells express a protein called the T cell

receptor, which will bind to only one or a few antigens out of the thousands that are possible.

• When a macrophage and a T cell encounter one another, they see whether any of the antigens on the surface of the macrophage fit into the T cell receptor.

• Most of the time the antigens don't fit.• If the antigens do match the T cell receptor, then the cells stick

to one another.• Through the action of chemical messengers, the T cell

becomes turned on, or activated. (discovery of BAch2)

B Cells• Last cell in the chain called in by the Activated T cells

• Each B cell is unique

• Instead of making specific surface proteins, B cells make proteins called antibodies that are released in the bloodstream

• These antibodies travel until they bind to the antigen that fits

• After an antigen is coated with antibodies, it is tagged for destruction

Other Important Facts on Immunity….

• Whether autoimmune disease will follow an autoimmune response depends upon both the quality of the immune response and the availability of the corresponding antigen.

• Antigens on the surface of circulating cells such as blood cells are readily available to circulating antibody, and therefore such cells may be damaged or eliminated by autoantibody acting with complement, killer T cells, or phagocytes.

• The receptors on cell surfaces such as the TSH receptor on the thyroid cell or on the acetylcholine receptor at neuromuscular junctions may also be directly attacked by autoantibody.

• This interaction may result in stimulating the receptor in Graves' disease or in blocking the neuromuscular transmission as observed in myasthenia gravis.

Autoimmunity and Enzymes

• In other diseases, autoantibodies are produced to particular enzymes

• For example, antibodies to the P450 enzymes are prominent in autoimmune hepatitis and primary biliary cirrhosis

• These enzymes are widely distributed in the body, and the question arises of why the diseases are organ-specific

• Evidence suggests that the enzymes are accessible to antibodies or T cells primarily in reactivated locations

Other Causes of Autoimmunity

• Other autoimmune diseases are not due to the direct effects of autoantibody

• They are associated with T-cell-mediated immune responses

• Cytotoxic T cells may be generated that can damage their respective target cell.

• In other cases, cytokines are produced that are harmful to surrounding tissue cells

Autoimmunity - Not Clear Cut!

• In human disease, it is frequently impossible to clearly separate the injury that is due to antibody-mediated from cell-mediated reactions.

• However, the cell-mediated responses are associated with the Th1 subset of CD4+ T cells

• This original simplistic view of the Th1/Th2 dichotomy is not easily applied to human disease in which both Th1 and Th2 responses are generally evident.

• In fact, some autoimmune diseases are actually down-regulated by administering interferon-gamma (IFN-g), the prototypic Th1 cytokine.

How Common are Autoimmune Diseases?

•Affect more than 23.5 million Americans

•Leading cause of death and disability

•Some autoimmune diseases are rare, while others, such as Hashimoto’s thyroiditis, affect many people.

•Some estimate that >50 million people have autoimmune disease as many cases are undiagnosed

•According to the AADRA (American Autoimmune Disease Related Association), there are @ 80-100 conditions that are autoimmune related.

Who Gets Autoimmune Diseases?

• People with a family history —Ex) lupus and multiple sclerosis. It is also common for different types of autoimmune diseases to affect different members of a single family. Inheriting certain genes can make it more likely to get an autoimmune disease. But a combination of genes and other factors may trigger the disease to start.

• People who are around certain things in the environment —Certain events or environmental exposures may cause some autoimmune diseases, or make them worse. Sunlight, chemicals called solvents, and viral and bacterial infections are linked to many autoimmune diseases.

Who Gets Autoimmune Diseases?

• People of certain races or ethnic backgrounds — Some autoimmune diseases are more common or more severely affect certain groups of people more than others. For instance, type 1 diabetes is more common in white people. Lupus is most severe for African-American and Hispanic people.

• Women of childbearing age — More women than men have autoimmune diseases, which often start during their childbearing years.

Types of Autoimmune Diseases

Alopecia areata

• The immune system attacks hair follicles (the structures from which hair grows). It usually does not threaten health, but it can greatly affect the way a person looks.

• Patchy hair loss on the scalp, face, or other areas of your body

Antiphospholipid Antibody Syndrome (aPL)

• A disease that causes problems in the inner lining of blood vessels resulting in blood clots in arteries or veins.

• Blood clots in veins or arteries

• Multiple miscarriages

• Lacy, net-like red rash on the wrists and knees


Autoimmune Hepatitis

• The immune system attacks and destroys the liver cells. This can lead to scarring and hardening of the liver, and possibly liver failure.

• Fatigue

• Enlarged liver

• Yellowing of the skin or whites of eyes

• Itchy skin

• Joint pain

• Stomach pain or upset


Celiac Disease

• A disease in which people can’t tolerate gluten, a substance found in wheat, rye, and barley, and also some medicines. When people with celiac disease eat foods or use products that have gluten, the immune system responds by damaging the lining of the small intestines.

• Abdominal bloating and pain

• Diarrhea or constipation

• Weight loss or weight gain

• Fatigue

• Missed menstrual periods

• Itchy skin rash

• Infertility or miscarriages


Diabetes Type 1

• A disease in which your immune system attacks the cells that make insulin, a hormone needed to control blood sugar levels. As a result, your body cannot make insulin. Without insulin, too much sugar stays in your blood. Too high blood sugar can hurt the eyes, kidneys, nerves, and gums and teeth. But the most serious problem caused by diabetes is heart disease.

• Being very thirsty / urinating often

• Feeling very hungry or tired

• Losing weight without trying

• Having sores that heal slowly

• Dry, itchy skin

• Losing the feeling in your feet or having tingling in your feet

• Having blurry eyesight


Graves’ Disease (Overactive Thyroid) • A disease that causes the thyroid to make too much thyroid hormone.

• Insomnia

• Irritability

• Weight loss

• Heat sensitivity

• Sweating

• Fine brittle hair

• Muscle weakness

• Light menstrual periods

• Bulging eyes

• Shaky hands

• Sometimes there are no symptoms


Guillain-Barre Syndrome

• The immune system attacks the nerves that connect your brain and spinal cord with the rest of your body. Damage to the nerves makes it hard for them to transmit signals. As a result, the muscles have trouble responding to the brain.

• Weakness or tingling feeling in the legs that might spread to the upper body

• Paralysis in severe cases

• Symptoms often progress relatively quickly, over a period of days or weeks, and often occur on both sides of the body.


Hashimoto’s Disease (underactive thyroid)

• A disease that causes the thyroid to not make enough thyroid hormone.

• Fatigue• Weakness• Weight gain Constipation • Sensitivity to cold• Muscle aches and stiff joints • Facial swelling


Hemolytic Anemia

• The immune system destroys the red blood cells. Yet the body can’t make new red blood cells fast enough to meet the body’s needs. As a result, your body does not get the oxygen it needs to function well, and your heart must work harder to move oxygen-rich blood throughout the body.

• Fatigue

• Shortness of breath

• Dizziness

• Headache

• Cold hands or feet

• Paleness

• Yellowish skin or whites of eyes

• Heart problems, including heart failure


Idiopathic Thrombocytopenic Purpura (ITP)

• A disease in which the immune system destroys blood platelets, which are needed for blood to clot.

• Very heavy menstrual period

• Tiny purple or red dots on the skin that might look like a rash.

• Easy bruising and/or Nosebleed or bleeding in the mouth


Inflammatory Bowel Disease (IBD)

• A disease that causes chronic inflammation of the digestive tract. Crohn’s (krohnz) disease and ulcerative colitis are the most common forms of IBD

• Abdominal pain

• Diarrhea, which may be bloody

Some people also have:

• Rectal bleeding

• Fever /Weight loss

• Fatigue /Mouth ulcers (in Crohn’s disease)

• Painful or difficult bowel movements (in ulcerative colitis)


Inflammatory Myopathies

• A group of diseases that involve muscle inflammation and muscle weakness. Polymyositis and dermatomyositis are 2 types more common in women than men.

• Slow but progressive muscle weakness beginning in the muscles closest to the trunk of the body. Polymyositis affects muscles involved with making movement on both sides of the body. With dermatomyositis, a skin rash comes before or at the same time as muscle weakness.

• Patients may also have:

• Fatigue after walking or standing

• Tripping or falling

• Difficulty swallowing or breathing


Multiple Sclerosis (MS)

• A disease in which the immune system attacks the protective coating around the nerves (myelin). The damage affects the brain and spinal cord.

• Weakness and trouble with coordination, balance, speaking, and walking

• Paralysis

• Numbness

• Tingling feeling in arms, legs, hands, and feet

• Symptoms vary because the location and extent of each attack vary


Myasthenia Gravis (MG)

• A disease in which the immune system attacks the nerves and muscles throughout the body.

• Double vision, trouble keeping a steady gaze, and drooping eyelids

• Trouble swallowing, with frequent gagging or choking

• Weakness or paralysis

• Muscles that work better after rest

• Drooping head

• Trouble climbing stairs or lifting things

• Trouble talking


Primary Biliary Cirrhosis

• The immune system slowly destroys the liver’s bile ducts. Bile is a substance made in the liver. It travels through the bile ducts to help with digestion. When the ducts are destroyed, the bile builds up in the liver and hurts it. The damage causes the liver to harden and scar, and eventually stop working.

• Fatigue

• Itchy skin

• Dry eyes and mouth

• Yellowing of skin and whites of eyes


Psoriasis

• A disease that causes new skin cells that grow deep in your skin to rise too fast and pile up on the skin surface.

• Thick red patches, covered with scales, usually appearing on the head, elbows, and knees

• Itching and pain, which can make it hard to sleep, walk, and care for yourself

• Patients may have a form of arthritis that often affects the joints and the ends of the fingers and toes. Back pain can occur if the spine is involved.


Rheumatoid Arthritis (RA) A disease in which the immune system attacks the lining of the joints throughout the body.

• Painful, stiff, swollen, and deformed joints

• Reduced movement and function

Patients may also have:

• Fatigue

• Fever

• Weight loss

• Eye inflammation

• Lung disease

• Lumps of tissue under the skin, often the elbows

• Anemia

• Increased risk of heart disease


Scleroderma

• A disease causing abnormal growth of connective tissue in the skin and blood vessels.

• Fingers and toes that turn white, red, or blue in response to heat and cold

• Pain, stiffness, and swelling of fingers and joints

• Thickening of the skin

• Skin that looks shiny on the hands and forearm

• Tight and mask-like facial skin

• Sores on the fingers or toes

• Trouble swallowing

• Weight loss

• Diarrhea or constipation

• Shortness of breath


Sjogren’s Syndrome

• A disease in which the immune system targets the glands that make moisture, such as tears and saliva.

• Dry eyes or eyes that itch

• Dryness of the mouth, which can cause sores

• Trouble swallowing

• Loss of sense of taste

• Severe dental cavities

• Hoarse voice

• Fatigue

• Joint swelling or pain

• Swollen glands

• Cloudy eyes


Systemic Lupus Erythematosus (ur-ih-thee-muh-TOH-suhss)

• A disease that can damage the joints, skin, kidneys, heart, lungs, and other parts of the body. Also called SLE or lupus.

• Fever

• Weight loss

• Hair loss

• Mouth sores

• Fatigue

• “Butterfly” rash across the nose and cheeks

• Rashes on other parts of the body

• Painful or swollen joints and muscle pain

• Sensitivity to the sun

• Chest pain

• Headache, dizziness, seizure, memory problems, or change in behavior


Vitiligo

• The immune system destroys the cells that give your skin its color. It also can affect the tissue inside your mouth and nose.

• White patches on areas exposed to the sun, or on armpits, genitals, and rectum

• Hair turns gray early• Loss of color inside your mouth


Polyarteritis Nodosa

Affects the smaller blood vessels throughout the body, causing fever, weight loss, headache, fatigue, muscle aches abdominal pain and blood in the urine

Giant Cell Arteritis

Affects the larger arteries leading to the head, causing fever, anemia, weakness, poor appetite and joint pain

Wegener’s Granulomatosis

Affects the smaller arteries and veins in the respiratory tract and kidneys, causing joint pain, poor appetite, weight loss, kidney failure, and weakness.

Kawasaki Disease

Causes swelling in the skin, redness of the lips, palms and mouth, swollen glands in the neck, and heart disease.

For people with autoimmune diseases, getting a proper diagnosis can be one of the most difficult

challenges they face.

• The American Autoimmune Related Diseases Association (AARDA) conducted a survey of autoimmune disease patients and found that the majority of those eventually diagnosed with serious autoimmune diseases had significant problems in getting a correct diagnosis.

• Many were incorrectly diagnosed with a variety of conditions that have no specific blood test to confirm the diagnosis.

• Many were told that their symptoms were in their heads or that they were under too much stress

• Further, the survey revealed that 45 percent of autoimmune disease patients had been labeled hypochondriacs in the earliest stages of their illnesses.

How Do We Diagnose Autoimmune Disease?

•History inc. family history

•Physical

•Blood tests

•Persistent patients


Tests for ANA: Amount of autoantibody presentTwo types of tests are commonly performed to detect and measure ANA:

1. Indirect Fluorescent Antibody (IFA)—the results of this method are reported as a titer. Titers are expressed as ratios. For example, the result 1:320 means that one part blood sample was mixed with 320 parts of a dilution.

2. Patterns of cellular fluorescence - In addition to a titer, positive results on IFA will include a description of the particular type of fluorescent pattern seen. Different patterns have been associated with different autoimmune disorders, although some overlap may occur. Some of the more common patterns include:• Homogenous (diffuse)—associated with SLE, MCTD, and drug induced lupus

• Speckled—associated with SLE, Sjogren syndrome, scleroderma, RA, MCTD and polymyositis

• Nucleolar—associated with scleroderma and polymyositis

• Centromere pattern (peripheral)—associated with scleroderma and CREST (Calcinosis, Raynaud syndrome, Esophogeal dysmotility, Sclerodactyly, Telangiectasia)


Tests for ANA

• About 3-5% of healthy Caucasians may be positive for ANA, and it may reach as high as 10-37% in healthy individuals over the age of 65 because ANA frequency increases with age.

• These would be considered false-positive results because they are not associated with disease.

Goals of Treatment

1. Relief of symptoms

2. Preservation of organ function

3. Targeting disease mechanisms

Overview of Traditional Medical Management

1. NSAIDS

2. Prednisone

3. DMARDS (Treating Rheumatoid Arthritis With Disease-Modifying Drugs)

4. Plasmaphoresis

5. IVIG (Intravenous immunoglobulin)

6. Monocolonal antibodies

7. Replace what is missing: cortisol, thyroid hormone, enzymes, Insulin, B12, etc.

8. Physical therapy

9. Surgery

New Breakthrough - The Off Switch??

• Scientists have made a major breakthrough in the fight against diseases such as multiple sclerosis and diabetes, by revealing how to stop cells attacking healthy body tissue.

• Rather than the body’s immune system destroying its own tissue by mistake, researchers at Bristol University have discovered how cells convert from being aggressive to actually protecting against disease.

• It’s hoped this latest insight will lead to the widespread use of antigen-specific immunotherapy as a treatment for many autoimmune disorders, including MS, type 1 diabetes and Graves’ disease.

• Bristol University revealed that effective treatment is achieved by gradually increasing the dose of antigenic fragment injected.

New Breakthrough - The Off Switch??

• Professor David Wraith, who led the research, said: “Insight into the molecular basis of antigen-specific immunotherapy opens up exciting new opportunities to enhance the selectivity of the approach while providing valuable markers with which to measure effective treatment. These findings have important implications for the many patients suffering from autoimmune conditions that are currently difficult to treat.”

• This treatment approach, which could improve the lives of millions of people worldwide, is currently undergoing clinical development through biotechnology company Apitope, a spin-out from the University of Bristol.

• The research was carried out by academics in Bristol University’s School of Cellular and Molecular Medicine and Department of Computer Science.

Read more at http://www.bristolpost.co.uk/Bristol-researchers-discover-new-way-treat-MS/story-22881849-detail/story.html#DypKvD4oE7ZR1PCY.99

What’s wrong with the traditional medicine approach?

• For most of these autoimmune disease conditions, the best that modern medicine can do is to keep some of the symptoms at bay

• The root cause of the condition is rarely, if ever, addressedby traditional medicine.

• In most cases, the source of autoimmunity can be traced to the overload of toxicity the body has had to deal with over many years.

NO DISEASE IS AN ISLANDNO DISEASE IS AN ISLAND

References

• Textbook of Functional Medicine; Jones, David MD(editor), 2006• Up to Date; Overview of autoimmunity; Rose, Noel R. 9/2013• AARDA -National Office 22100 Gratiot Ave. Eastpointe, MI

48021 586.776.3900 586.776.3903 (fax)• U.S. Department of Health and Human Services. Office on Women’s Health.

Women’s Health Issues: An Overview. Fact sheet. May 2000.

Health & Medicine

Introduction Autoimmune Disease by Dr. Kelly Cobb