FACTS, FOR CONTENT:

 

AUTOIMMUNE SCIENCE
Dr. Sarah Ballantyne, PhD

WHAT IS AUTOIMMUNE DISEASE?

  • Anyof>140diseasescausedbytheimmunesystem attacking tissues in the human body

  • Difficulttodiagnose
    (45% of patients later diagnosed with a serious a autoimmune disease are labeled as hypochondriacs in the early phases of their diseases)

  • Chronicandlifelong(nocure)

  • Medicaltreatmentsarelimited;

symptom management

  • Affects~50millionAmericans

  • Incidenceinincreasing

WHY FOCUS ON AUTOIMMUNE DISEASE?

• Ournation’sbiggesthealthobstacle

• Fewestavailablemedicalinterventions

• Highdirecthealthcarecosts,andevenhigherindirect health care costs

WHAT CAUSES AUTOIMMUNE DISEASE?

WHAT IS AUTOIMMUNE DISEASE?

Autoimmune Disease

COMMON AUTOIMMUNE DISEASES

• Hashimoto’s thyroiditis: up to 1 in 34
An autoimmune condition in which the thyroid
does not make enough hormones for the body's needs

• Sjögren's syndrome: up to 1 in 29
An autoimmune system disorder characterized by dry eyes and dry mouth.

• Celiac disease: up to 1 in 53
An immune reaction to eating gluten, a protein found in wheat, barley, and rye.

• Alopecia areata: up to 1 in 59
Sudden hair loss that starts with one or more circular bald patches that may overlap.

J Autoimmun. 2009 Nov–Dec; 33(3-4): 197–207.

COMMON AUTOIMMUNE DISEASES

• Psoriasis: up to 1 in 65
A condition in which skin cells build up and form scales and itchy, dry patches.

• Type 1 diabetes: up to 1 in 106
A chronic condition in which the pancreas produces little or no insulin.

• Rheumatoid arthritis: up to 1 in 123
A chronic inflammatory disorder affecting many joints, including those in the hands and feet.

• Polymyalgia rheumatic: up to 1 in 135
An inflammatory disorder causing muscle pain and stiffness around the shoulders and hips.

J Autoimmun. 2009 Nov–Dec; 33(3-4): 197–207.

COMMON AUTOIMMUNE DISEASES

• Grave’s disease: up to 1 in 160
An autoimmune disorder that results in the overproduction of thyroid hormones.

• Multiple sclerosis: up to 1 in 279
A disease in which the immune system eats away at the protective covering of nerves.

• Ulcerative colitis: up to 1 in 264
A disease that causes inflammation and sores (ulcers) in the lining of the large intestine

• Crohn’s disease: up to 1 in 444
A type of inflammatory bowel disease (IBD) that may affect any part of the gastrointestinal tract.

J Autoimmun. 2009 Nov–Dec; 33(3-4): 197–207.

FREQUENT CO-MORBIDITIES

  • Cholangitis

  • Chronic fatigue syndrome

(suspected autoimmune disease)

  • Eczema

  • Fibromyalgia

(suspected autoimmune disease)

• Polycystic ovary syndrome (PCOS)
(frequently in conjunction with autoimmune thyroid diseases)

WHAT IS AUTOIMMUNE DISEASE?

  • Anyof>140diseasescausedbytheimmunesystem attacking tissues in the human body

  • Difficulttodiagnose
    (45% of patients later diagnosed with a serious a autoimmune disease are labeled as hypochondriacs in the early phases of their diseases)

  • Chronicandlifelong(nocure)

  • Medicaltreatmentsarelimited;

symptom management

  • Affects~50millionAmericans

  • Incidenceinincreasing

AUTOIMMUNE DISEASE IS ON THE RISE

N Engl J Med. 2002 Sep 19;347(12):911-20.

AUTOIMMUNE DISEASE IS ON THE RISE

The net % increase/year of the incidence and prevalence of autoimmune diseases worldwide

Int. J. of Celiac Disease, 2015, Vol. 3, No. 4, 151-155.

78% OF SUFFERERS ARE WOMEN

Emerg Infect Dis. 2004 Nov; 10(11): 2005–2011.

EARLY SYMPTOMS OF AUTOIMMUNE DISEASE

• PMS
• Rashes and other skin problems • Recurrent headaches
• Resistance to weight loss
• Sleep disturbances
• Susceptibility to infections
• Swollen glands
• Thyroid problems
• Unexplained weight changes
• Yeast infections

• Allergies

• Anxiety and depression

• Blood pressure changes (usually low)

  • Digestive problems

  • Extreme fatigue

  • Gallbladderdisease

  • Low blood sugar

  • Malaise

  • Memory problems

  • Migraines

  • Muscle or joint pain

  • Muscle weakness

WHAT CAUSES AUTOIMMUNE DISEASE?

THE IMMUNE SYSTEM IN AUTOIMMUNE DISEASE

Autoimmune disease occurs when:

• autoantibodies form (=autoimmunity, occurring in ~30% of us),

• the body’s natural backup system for eliminating/regulating cells that produce autoantibodies fails,

• the immune system is stimulated to attack, and

• enough damage occurs to cells or tissues within the body to manifest as symptoms of a disease.

IMMUNE SYSTEM REVIEW

IMMUNE SYSTEM REVIEW

REGULATORY VS EFFECTOR CELLS

THE IMMUNE SYSTEM IN AUTOIMMUNE DISEASE

Autoimmune disease occurs when:

autoantibodies form (=autoimmunity, occurring in ~30% of us),

• the body’s natural backup system for eliminating/regulating cells that produce autoantibodies fails,

• the immune system is stimulated to attack, and

• enough damage occurs to cells or tissues within the body to manifest as symptoms of a disease.

AUTOANTIBODY FORMATION

AUTOANTIBODY FORMATION

AUTOANTIBODIES IN CANCER

Autoimmunity Reviews, Volume 15, Issue 5, 2016, 477–483

AUTOANTIBODY FORMATION

J Clin Invest. 2015;125(6):2194-2202.

INFECTION AS A SOURCE OF AUTOANTIBODIES

  • Prior infections increase risk of specific autoimmune diseases, perhaps via cross-reactive antibody formation.

  • Borrelia: spirochete bacteria typically transmitted by lice and ticks.

• Lyme disease, rheumatoid arthritis, sarcoidosis, schizophrenia* and

• Chlamydophila pneumoniae: bacteria that causes pharyngitis, bronchitis, and atypical pneumonia

• Arthritis, myocarditis, Guillain-Barré syndrome, Alzheimer’s disease*, chronic fatigue syndrome*, chronic obstructive pulmonary disease*, multiple sclerosis, and Tourette syndrome

• Enterovirus: viruses of the gastrointestinal tract that cause a wide range of diseases

• Amyotrophic lateral sclerosis*, chronic fatigue syndrome*, type 1 diabetes, Guillain-Barré syndrome, and schizophrenia*

dementia*

INFECTION AS A SOURCE OF AUTOANTIBODIES

• Giardia lamblia: parasite that causes “beaver fever” or “backpacker’s diarrhea”

• multiple sclerosis, amyotrophic lateral sclerosis*, Parkinson’s disease*, chronic fatigue syndrome*, arthritis, and uveitis

• Helicobacter pylori: bacteria that causes chronic gastritis, stomach ulcers, and linked to stomach cancer

• immune thrombocytopenia, psoriasis, and sarcoidosis

  • Herpesvirus: virus family causing wide range of illness, such as mononucleosis and roseola

    • Cytomegalovirus: Guillain-Barré syndrome and systemic lupus erythematosus

    • Epstein-Barr virus: dermatomyositis, systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, and multiple sclerosis

    • Human herpesvirus 6: multiple sclerosis, chronic fatigue syndrome*

  • Norovirus: virus causing gastroenteritis

• Crohn’s disease

INFECTION AS A SOURCE OF AUTOANTIBODIES

• Parvovirus B19: virus causes a childhood rash called fifth disease and a form of acute arthritis.

• rheumatoid arthritis, systemic lupus erythematosus and vasculitis. • Streptococcus: bacteria causing strep throat?

• Tourette syndrome
• Toxoplasma gondii: parasite causing toxoplasmosis

• Alzheimer’s disease*, Parkinson’s disease*, Tourette syndrome, antiphospholipid syndrome, systemic sclerosis, and inflammatory bowel diseases

THE IMMUNE SYSTEM IN AUTOIMMUNE DISEASE

Autoimmune disease occurs when:

• autoantibodies form (=autoimmunity, occurring in ~30% of us),

the body’s natural backup system for eliminating/regulating cells that produce autoantibodies fails,

• the immune system is stimulated to attack, and

• enough damage occurs to cells or tissues within the body to manifest as symptoms of a disease.

ACTIONS OF REGULATORY T CELLS

IMMUNE HOMEOSTASIS

LOSS OF IMMUNE REGULATION

Nature Reviews Immunology 10, 849-859 (Dec 2010)

LOSS OF IMMUNE REGULATION

ROLE OF GENETICS

• RAG-1 and RAG-2

  • controls receptor editing on B cells when they fail autoreactivity test

  • severe combined immunodeficiency (SCID)

    • FoxP3

  • intracellular molecule called regulatory T-cells

  • mutations prevent regulatory T cell development

  • immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX).

• Sialic acid acetylesterase (SIAE)
• enzyme that decreases B cell receptor signaling required for immune

tolerance

  • SIAE required to suppress autoreactive B

  • present in 2% of those with autoimmune disease

  • rheumatoid arthritis and type 1 diabetes

ROLE OF GENETICS

  • Enzyme 3' repair exonuclease 1 (Trex1)

    • proofreading function for DNA synthesis

    • component of interferon-stimulatory response to detected viral DNA

    • Aicardi-Goutières syndrome (AGS) and chilblain

  • PTPN22

    • encodes tyrosine phosphatase, nonreceptor type 22 (lymphoid)

    • affects the responsiveness of T and B cell receptors

    • R620W: type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, vitiligo, and Graves’ disease

ROLE OF GENETICS

  • Methylenetetrahydrofolate reductase (MTHFR)

    • rate-limiting enzyme in the methyl cycle

    • methyl groups are used to control the activity of a huge variety of proteins through the post-translational modification methylation, cortisol, melatonin, epinephrine and serotonin

    • defects cause buildup of homocysteine, a toxic nonprotein amino acid

    • increases inflammation

    • C667T and A1298C: type 1 diabetes, Hashimoto’s thyroiditis, Graves’ disease, rheumatoid arthritis, vitiligo, multiple sclerosis Alzheimer’s disease* and schizophrenia* (also cardiovascular disease, renal disease, neurodegenerative disease, osteoporosis, and cancer).

  • Human leukocyte antigen (HLA)

    • encodes many immune response genes

    • encodes the major histocompatibility complex

    • many variants linked to autoimmune disease

ROLE OF GENETICS: HLA

ROLE OF GENETICS: HLA

• HLA-B27: ankylosing spondylitis, postgonococcal arthritis, acute anterior uveitis, reactive arthritis (Reiter’s syndrome), seronegative spondyloarthropathy, iritis, psoriatic arthritis, Crohn’s disease and ulcerative colitis, and ulcerative colitis–associated spondyloarthritis

• HLA-B8: Grave’s disease

• HLA-B47: 21-hydroxylase deficiency 15

• HLA-DR2: systemic lupus erythematosus

• HLA-DR3: autoimmune hepatitis, primary Sjögren syndrome, Grave’s disease

• HLA-DR3 and HLA-DR4: type 1 diabetes mellitus, Hashimoto’s thyroiditis

• HLA-DQ2 and HLA-DQ8: celiac disease, Hashimoto’s thyroiditis, primary Sjögren syndrome

  • HLA-DQ5: scleroderma

  • HLA-DQ7: Hashimoto’s thyroiditis

THE IMMUNE SYSTEM IN AUTOIMMUNE DISEASE

Autoimmune disease occurs when:

• autoantibodies form (=autoimmunity, occurring in ~30% of us),

• the body’s natural backup system for eliminating/regulating cells that produce autoantibodies fails,

• the immune system is stimulated to attack, and

• enough damage occurs to cells or tissues within the body to manifest as symptoms of a disease.

WHAT STIMULATES THE IMMUNE SYSTEM?

  • Infection

  • Toxinexposureand/orpoordetoxification

  • Gutdysbiosis;increasedintestinalpermeability

  • Stress

  • Insufficientsleep

  • Beingsedentaryorengaginginexhaustiveintense activity

  • Nutrientdeficiencies(vitaminD,iron,zinc,etc.)

  • Inflammatorydiet(sugars,sweeteners,omega-6fats, oxidized fats, processed food chemicals, preservatives, food dyes, and various inflammatory compounds in grains, legumes, dairy, nightshades)

INFECTION STIMULATES IMMUNE RESPONSES

REGULATORY VS EFFECTOR CELLS

Nature Reviews Immunology 13, 607–614 (2013)

PERSISTENT INFECTIONS

• Helicobacter pylori:
• interacts with the immune system by influencing which cytokines are

produced by macrophages, B cells, and T cells

• drives Th1 formation or Th2 formation, but usually the former, and can cause rapid switching between Th1 and Th2

  • stimulates recruitment of inflammatory cells, such as neutrophils

  • induce changes in gastric-acid secretion by the cells that line the stomach

and alter the secretion of mucus by the cells that line the small intestine

• chronic gastritis (inflammation of the stomach and upper digestive tract) increasing intestinal permeability (i.e., leaky gut)

• Toxoplasmosis gondii:
• 29% of healthy individuals have antibodies against T. gondii but 42% of

those with autoimmune disease do

  • damages intestinal barrier and induces potent Th1 response

  • inhibits macrophages and dendritic cells causing chronic secondary inflammation and immune activation

PERSISTENT INFECTIONS

• Cell wall–deficient bacteria:
• a class of antibiotic-resistant bacteria that can remain latent or slow-

growing within human cells for extended periods

  • have been found in patients with sarcoidosis and systemic lupus erythematosus.

  • may contribute to autoimmune disease by releasing endotoxin into phagocytes, causing release of cytokines that stimulates Th1 cells

TOXIN EXPOSURE

• Prescription drugs

• 38 drugs linked to lupus (drug-induced lupus erythematosus)

  • hydralazine (a blood-pressure medication),

  • procainamide (used to treat cardiac arrhythmias)

  • isoniazid (an antibiotic used to treat tuberculosis)

• Pristane
• naturally occurring hydrocarbon found in petroleum that is commonly

used as a lubricant, an immunologic adjuvant, and an anticorrosion agent • rheumatoid arthritis and systemic lupus erythematosus.

• Silica dust
• occupational hazard for workers in mining, stone cutting, quarrying,

blasting, road and building construction, and farming, • systemic sclerosis

• Smoking
• seropositive rheumatoid arthritis

TOXIN EXPOSURE

• Pesticides

  • occupational exposure, gardening

  • most are immunotoxic

• organochlorinated pesticides (mostly illegal): increase proinflammatory cytokines, decrease neutrophil and natural-killer-cell function, decrease regulatory T-cell populations, decrease cytotoxic T cell populations, alter the ratio of CD4+ and CD8+ cells, and increase autoantibody formation.

• organophosphates and carbamates (widely-used insecticides): changes the ratios of CD4+ and CD8+ T cells, including influencing Th1 versus Th2 dominance, but also inhibiting the activities of neutrophils and natural killer cells.

• tributyltin chloride (an organotin pesticide): causes thymocyte death in the thymus gland

• atrazine (an organotin pesticide): decreases natural- killer-cell activity

• propanil: decreases T cells and B cells (thymus and bone marrow); reduces natural killer cells, macrophages, and cytokine production; and causes thymic atrophy

TOXIN EXPOSURE

  • Ultraviolet radiation

    • multiple sclerosis (inverse relationship, independent of vitamin D)

    • dermatomyositis

  • Heavy metals

    • mercury, cadmium, lead, aluminum, and gold

    • strongly linked to autoimmune disease

  • Poor detoxification (MTHFR variants)

    • methylation used in Phase 2 liver detoxification (conjugation)

    • C667T and A1298C: type 1 diabetes, Hashimoto’s thyroiditis, Graves’ disease, rheumatoid arthritis, vitiligo, multiple sclerosis Alzheimer’s disease* and schizophrenia* (also cardiovascular disease, renal disease, neurodegenerative disease, osteoporosis, and cancer).

GUT HEALTH AND THE IMMUNE SYSTEM

• Leaky gut
• considered a prerequisite for

autoimmune disease to develop
• present in every autoimmune disease that has

been tested: rheumatoid arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, celiac disease, multiple sclerosis, and type 1 diabetes.

• precedes disease development for celiac disease, Crohn’s disease, and
ulcerative colitis

GUT HEALTH AND THE IMMUNE SYSTEM

GUT HEALTH AND THE IMMUNE SYSTEM

• Gut microbiota

  • aid digestion and increase nutrient absorption

  • synthesize vitamins

  • produce SCFA

  • produce neurotransmitters

  • regulate the immune system

• Gut dysbiosis

• any abnormality in the gut microbiota, eg. SIBO

• commonly seen in autoimmune disease

• different bacterial components modulate different aspects of the immune system

• balance Th1, Th2, and Th3 cell populations through regulation of dendritic cell activation

• stimulate the production of Th17 cells

• modulate the activation of natural killer cells

• influence the interaction between antigen receptors on the immune cell surfaces and the antigens themselves

• stimulating the production of antibodies against foreign microorganisms.

STRESS AND THE IMMUNE SYSTEM

Image credit: livelovefruit.com

STRESS AND THE IMMUNE SYSTEM

• Chronic Stress (via cortisol, cortisol resistance, CRH)

  • Increases inflammation

  • Affects T-cell subsets (situation dependent)

  • Increases intestinal permeability

  • Decreases gut motility

  • Decreases mucus

production by goblet cells

  • Decreases secretory IgA

  • Inhibits digestion (pancreatic enzyme secretion, gall bladder function)

  • Decreases intestinal blood flow

  • Alters gut microbiome

  • Reduces sleep quality

SLEEP AND THE IMMUNE SYSTEM

SLEEP AND THE IMMUNE SYSTEM

  • Insufficient sleep

    • increases monocytes, neutrophils, and B cells in the blood

    • increases proinflammatory cytokines (including cytokines known to stimulate maturation of naïve T cells into Th1, Th2, and Th17 cells),

    • increases C-reactive protein

    • increases total cholesterol LDL.

  • Non-apnea sleep disorders (eg. insomnia) increases risk of autoimmune disease by 50%

  • Obstructive sleep apnea more than doubles risk of autoimmune disease

  • Shift work increases risk by 50%

  • Short sleep increases symptoms of many autoimmune diseases

ACTIVITY AND THE IMMUNE SYSTEM

ACTIVITY AND THE IMMUNE SYSTEM

• Exercise training reduces levels of proinflammatory cytokines in adipose tissue.

• Exercise may reduce inflammation by decreasing lipid accretion in liver and muscle.

• Lipid accumulation is linked to inflammation in a setting of nutrient overload.

• Anti-inflammatory effects may be mediated via inhibition of TLR
and IL-1 signaling.

Trends in Immunology Volume 35, Issue 6, p262–269, June 2014

NUTRIENT DEFICIENCY AND THE IMMUNE SYSTEM

  • Vitamin A: immune regulator, differentiation

  • Vitamin D: immune regulator, Treg cells

  • Vitamin E: antioxidant

  • Vitamin K2: antioxidant

  • Vitamin B6: methylation

  • Vitamin B9 (folate): methylation

  • Vitamin B12: cell production, methylation

  • Vitamin C: antioxidant

  • Zinc: T-cell development and activation, cytokines

  • Selenium: antioxidant, cell function and activation

  • Iodine: phagocyte health

  • Iron: antioxidant enzymes

  • Magnesium: thymus gland

  • Copper: cytokine production, cell proliferation

  • Phytochemicals: antioxidants

  • Omega 3 fats: phagocytes

NUTRIENT DEFICIENCY AND THE IMMUNE SYSTEM

  • Vitamin A: alopecia areata, multiple sclerosis, and autoimmune hepatitis

  • Vitamin D: systemic lupus erythematosus, type 1 diabetes, autoimmune interstitial lung disease, multiple sclerosis, rheumatoid arthritis, celiac disease, psoriasis, and inflammatory bowel disease

  • Vitamin E: psoriasis, vitiligo, alopecia areata, and rheumatoid arthritis

  • Vitamin K2: supplementation beneficial in an animal model of multiple

  • Vitamin B6: type 1 diabetes

  • Vitamin B9: cerebral folate deficiency syndrome, rheumatoid arthritis, Sjogren's syndrome, celiac disease, Crohn's disease and ulcerative colitis

  • Vitamin B12: multiple sclerosis, celiac disease, Sjogren's syndrome, Crohn's disease, ulcerative colitis, autoimmune atrophic gastritis, alopecia areata and type 1 diabetes

  • Vitamin C: lichen planus, and idiopathic thrombocytopenic purpura

  • Zinc: rheumatoid arthritis, multiple sclerosis, pemphigus vulgaris, Alzeimer’s disease, autoimmune hepatitis, primary biliary cirrhosis, autoimmune thyroid disease, systemic lupus erythematosus, celiac disease and type 1 diabetes

NUTRIENT DEFICIENCY AND THE IMMUNE SYSTEM

• Selenium: Hashimoto’s thyroiditis, Grave’s disease, pemphigus vulgaris and lichen planus

  • Iodine: Hashimoto’s thyroiditis, Grave’s disease

  • Iron: rheumatoid arthritis, autoimmune gastritis, systemic lupus

erythematosus, Sjogren's syndrome and celiac disease

  • Magnesium: systemic lupus erythematosus

  • Copper: rheumatoid arthritis and pemphigus vulgaris

  • Phytochemicals: supplementation beneficial in autoimmune thyroiditis, type 1 diabetes, and rheumatoid arthritis

  • Omega 3 fats: supplementation beneficial in rheumatoid arthritis, Crohn’s disease, ulcerative colitis, psoriasis, systemic lupus erythematosus, multiple sclerosis, autoimmune-mediated glomerulonephritis

INFLAMMATORY DIETS

  • Prolamins: increase intestinal permeability, feed bacterial overgrowth in the gut, and stimulate the immune system

  • Agglutinins: increase intestinal permeability, feed bacterial overgrowth in the gut, and stimulate the immune system

  • Saponins/Glycoalkaloids: increase intestinal permeability and significantly stimulate the immune system

  • Antinutrients: causes increased intestinal permeability, feed gut dysbiosis, and cause inflammation

  • Digestive Enzyme Inhibitors: increase intestinal permeability, feed bacterial overgrowth in the gut, and cause inflammation.

  • Processed food chemicals: causes increased intestinal permeability, feed gut dysbiosis, and cause inflammation

INFLAMMATORY DIETS

  • Sugar and sweeteners: increase intestinal permeability, causes inflammation, and causes hormone dysregulation

  • High Omega-6 relative to Omega-3 fatty acids: cause inflammation and gut dysbiosis

  • Alcohol: increased intestinal permeability, damages the gut, feeds bacterial overgrowth in the gut, and stimulates inflammation

THE IMMUNE SYSTEM IN AUTOIMMUNE DISEASE

Autoimmune disease occurs when:

• autoantibodies form (=autoimmunity, occurring in ~30% of us),

• the body’s natural backup system for eliminating/regulating cells that produce autoantibodies fails,

• the immune system is stimulated to attack,

and

• enough damage occurs to cells or tissues within the body to manifest as symptoms of a disease.

WHAT CAUSES AUTOIMMUNE DISEASE?

• Geneticsusceptibility(1/3ofyourriskfor autoimmune disease)

• Infection,environmentaltriggers,orbadluck • Dietandlifestyle

Immune Dysregulation (the body attacks itself)

THE IMMUNE SYSTEM IN AUTOIMMUNE DISEASE

Autoimmune disease occurs when:

and

• autoantibodies form (=autoimmunity, occurring in ~30% of us),

• the body’s natural backup system for eliminating/regulating cells that produce autoantibodies fails,

• the immune system is stimulated to attack,

enough damage occurs to cells or tissues within the body to manifest as symptoms of a disease.

AUTOIMMUNE DISEASE

Autoimmune Disease

WHAT IS AUTOIMMUNE DISEASE?

All autoimmune diseases are caused by a betrayal of the immune system. The immune system,

which is supposed to protect us from invading microorganisms, instead targets normal proteins within our own bodies, treating these fundamental components of our cells with the exact same lethal force as it would a virus, bacteria, or parasite.

Antibodies are an essential part of the immune system that recognize specific proteins in foreign cells, like pathogens. By binding to them, they signal to immune cells that there is something to attack.

With autoimmune disease, the body accidentally creates antibodies that identify not only foreign proteins, but the body’s own proteins—these are called autoantibodies (antibodies that target “self”). The formation of antibodies to the body’s own tissues is the first crucial step in the development of autoimmune disease.

The signs and symptoms of autoimmune disease are present when the immune system’s attack of tissues impacts the regular functioning of the body. They can impact any organ or system of the body.

Autoimmune Disease Facts:

  • Autoimmune disease is estimated to affect more than 50 million Americans or 20% of the population (compared with 12 million with cancer and 25 million with heart disease)

  • Autoimmune disease affects more women than men, with 75% of patients being female

  • There are more than 100 confirmed autoimmune diseases, with many more diseases

    suspected to be autoimmune in nature

  • The prevalence of autoimmune disease is steadily increasing

  • Autoimmune disease is caused partly by genetics and runs in families

  • Having one autoimmune disease increases the chance of developing more autoimmune diseases

  • Diagnosing autoimmune disease is challenging, because early symptoms often present as vague signs that can be dismissed

  • Up to 45% of those with autoimmune disease are labeled as hypochondriacs in the earliest stages of illness

  • The average time it takes to get an autoimmune disease diagnosis is 4.6 years and 5 doctors

  • There is no medical specialty devoted to the diagnosis and treatment of autoimmune disease

    in general

  • Conventional medicine offers no cure for autoimmune disease; treatment is based on symptom management only

  • Treating autoimmune disease is estimated to cost over $100 billion dollars annually

  • Evidence, including medical trials, is accumulating for the inclusion of natural approaches to managing autoimmune disease, like dietary and lifestyle modifications

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WHAT CAUSES AUTOIMMUNE DISEASE?

Genetics

The genes you inherit from your parents play a part in determining your predisposition for developing an autoimmune disease, and because of this, it is very common for them to run in families. For instance, the incidence of celiac disease in the general population is 1 in 100 people, while the incidence in those with a first-degree family member who has it, like parents, siblings, or children, is 1 in 22.

Unlike genetic diseases, however, where one or two gene mutations are responsible for the disease, there are countless genes that affect your risk for autoimmune disease. Instead of inheriting one specific autoimmune gene, you inherit a larger collection that puts you at risk for developing an autoimmune disease. This may place you at more or less risk for certain diseases and it is why specific ones are not always inherited in families, but many members of the same family suffer from different related diseases.

Environmental Triggers

Although it can be handy to blame autoimmune disease all on genetics, it only accounts for about one- third of your risk of developing one. It is often said that while genes load the gun, environment pulls the trigger. Pathogens, chemicals, and substances your immune system is exposed to in your daily life can have an impact on whether or not you develop an autoimmune disease.

Certain bacterial and viral infections, both acute and chronic, have been linked to the development of autoimmunity—most likely because they contain proteins that closely resemble your own, easily confusing the immune system. Exposure to toxins and chemicals can similarly trigger autoimmunity. You are exposed to these compounds through pollution, the water supply, pesticides and herbicides in foods, cleaning products, personal-care products, chemical exposure at home or work, and more.

Diet and Lifestyle

A poor diet contributes to the development of autoimmune disease by exacerbating intestinal permeability, creating nutrient deficiencies, and over-activating the immune system. Similarly, sleep issues, lack of movement, and drug exposure, both prescription and recreational, can also increase your risk of developing an autoimmune disease. Stress also plays an important part in the autoimmune disease process. People experiencing acute and unmanaged stress or chronic stress are often at a higher risk for developing autoimmune disease.

Finally, your geographic location may play a role. For example, in the US, it has been shown that those living in the Pacific Northwest have a higher incidence of certain autoimmune diseases, which may in part be due to a lack of natural sunlight at higher latitudes, contributing to vitamin D deficiency.

Takeaway: While you can’t do much about your genetic influence and exposure to infectious disease, you can do something about managing your dietary and lifestyle choices, as well as limiting your contact with toxins and chemicals!

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BUILDING RESILIENCE

Although at first it can seem cut and dry to receive an autoimmune diagnosis, it is rarely that simple. Most people will experience a range of complex emotions following diagnosis. However, most people facing autoimmune disease eventually navigate this emotional challenge successfully using the skills associated with resiliency.

Resilience is a set of skills that gives us the ability to withstand stress and adversity, including the stresses and difficulties of a life-changing autoimmune diagnosis. Importantly, you should know that resilience is not a personality trait we are born with, it is a set of skills that can be learned and with practice can become second-nature.

Six skills that build resilience:

MAINTAIN A POSITIVE SELF-IMAGE

Have confidence in your strengths and abilities and view yourself as a survivor, rather than a victim, of autoimmune disease.

MANAGE EMOTIONS AND IMPULSES

Don’t freak out! Although a crisis may at first seem overwhelming, take time to adjust yourself and then react in a calm, composed manner. This is more effective than losing it.

TAKE CHARGE OF THINGS IN YOUR CONTROL

Try to actively problem solve, communicate clearly with those around you, and seek resources that can help you.

ESTABLISH HEALTHY VERSUS HARMFUL COPING STRATEGIES

Find ways to laugh, exercise, pray or meditate, consider talk therapy (if appropriate), or spend time with loved ones versus engage in harmful strategies like abusing alcohol or drugs.

INVEST IN CLOSE RELATIONSHIPS

Invest in close relationships if you are lacking them or devote time to the important ones that already exist. These relationships together function as a crucial support system that allows you to ask for help and give help.

FIND POSITIVE MEANING IN LIFE EVENTS

Reframe negative situations to see their value or the favorable effects these situations may have had on you as a person.

Takeaway: Don’t allow your diagnosis to discourage you; instead, incorporate resilience into your response to the new information you have received. This crucial information allows you to move towards wellness!

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WHY DO I NEED A DIAGNOSIS?

Many of us who suffer from autoimmune symptoms wonder why we should even bother seeking a diagnosis, especially if our symptoms can improve just by making dietary and lifestyle changes. However, as you can see from the list below, there are benefits to having a clear diagnosis.

The benefits of having a diagnosis:

  1. It helps you connect with the right medical specialist for your condition.

  2. It helps medical practitioners decide which testing to pursue regularly to gauge progress.

  3. It helps you and your doctor decide which treatment option (medication, surgical, or other) is best for you.

  4. It helps you connect with others who are suffering from the same condition.

  5. It helps complementary care practitioners tailor their programs and protocols specifically to your needs.

  6. It enables you to research and educate yourself about your disease.

  7. It helps you and your doctor practice good preventative care, anticipating issues and being able to order the right testing to gauge progress.

  8. It helps you understand what your disease progression might look like as well as signs and symptoms to be aware of.

  9. It gives you peace of mind knowing what is causing your symptoms.

What if I can’t get a diagnosis?

Sometimes patients suffer from chronic symptoms that could be autoimmune in nature, but can’t obtain a diagnosis for one reason or another. This might be due to:

  • lack of access to medical care

  • poor quality medical care

  • lack of financial resources

  • not being able to find a collaborative physician

    Although it is recommended that every patient who suspects an autoimmune condition prioritize getting a diagnosis, some patients forgo the diagnosis process after discovering that they can manage their illness with dietary and lifestyle modifications.

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Overlapping diagnosis

It is common for those who have one autoimmune disease already to get a diagnosis of additional autoimmune diseases during their lifetime. Adding to this, symptoms of some autoimmune conditions are similar to others, which is known as overlap. This occurs most in the autoimmune conditions that affect connective tissue, such as:

  • Rheumatoid arthritis

  • Scleroderma

  • Raynaud’s syndrome

  • Mixed connective tissue disease

  • Sjoren’s syndrome

  • Lupus

    Some autoimmune conditions frequently coexist with others, like Hashimoto’s and Grave’s disease or Hashimoto’s and celiac disease.

    These symptom and disease overlaps can make it difficult to obtain an accurate diagnosis and proper treatment. Patients with multiple autoimmune conditions often see different specialists to manage each one. In the case of multiple autoimmune diagnosis the disease with the most severe symptoms is usually given treatment preference.

    Common misdiagnoses

    Because autoimmune disease can cause non-specific symptoms that overlap with many conditions, patients can often be misdiagnosed with other, non-autoimmune conditions, or they may not be suffering from an autoimmune condition in the first place. It is important to be aware of these diseases that can produce similar symptoms, in addition to the fact that a person can suffer from autoimmune disease in combination with other non-autoimmune conditions.

    Here is a list of conditions that are commonly confused with autoimmune disease:

  • Chronic fatigue syndrome

  • Lyme disease (can result in autoimmunity)

  • Fibromyalgia

  • Alzheimer’s or Parkinson’s disease

  • Irritable bowel syndrome

  • Nutrient deficiency (like anemia)

  • Mental disorders like depression, anxiety, and bipolar disorder

  • Sleep apnea

  • Chronic infection (can trigger autoimmunity)

  • Migraines

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AUTOIMMUNE STATUS SELF-TEST

This test can help you evaluate where you are at right now on the autoimmune spectrum. The point is not to dwell on your current experience, but to work with your practitioner to make the best choices about where to go next in terms of diagnosis, treatment, and lifestyle changes.

Instructions: You will find two sections, the first with the same scoring for each question, and the second with an individual scoring system per question. At the end of the test, you will add the scores from both sections to come up with your autoimmune status. From there, you will have some information to guide the next steps in your healing journey. You can also come back to section one of this test once you have made some changes to gauge your healing progress over time.

Section 1

Mark the blank with the number that best corresponds to how frequently you experience that symptom.

SCORING:

0=never occurs 1=occurs rarely (monthly)

  • _  fatigue and lack of energy

  • _  chronic pain—muscles, joints, and bones

  • _  heaviness in limbs, loss of muscle tone

2=occurs occasionally (weekly) 3=occurs frequently (daily)

  • _  trouble falling or staying asleep

  • _  cold hands or feet and have trouble staying warm

  • _  heat intolerance and/or sun sensitivity

  • _  rapid heartbeat

  • _  night sweats

  • _  difficulty swallowing, hoarseness, lump in the throat

  • _  decreased sense of taste or smell

  • _  difficulty concentrating or focusing (brain fog)

  • _  thinning hair or hair loss

  • _  loss of outer 1⁄3 of eyebrow

  • _  numbness or tingling in extremities

  • _  dizziness or lightheadedness

  • _  food allergies/sensitivities

  • _  dark circles under eyes

  • _  unexplained low-grade fever

  • _  periodontal infections or gum issues

_

_

_

_

morning stiffness weakness and/or tremor headaches
feeling puffy or inflamed

_ rashes, hives and skin issues of unknown origin

_

_

_

_

_

_

_

_

_

dry eyes, mouth or skin

dermatitis or itchy skin

white patches on skin or inside of the mouth

mouth ulcers

trouble maintaining a healthy weight

difficulty with exercise

IBS, or “irritable bowel syndrome” (constipation, diarrhea, or both)

abdominal pain or stomach cramps blood or mucus in stool

_ Total for Section 1 (keep this handy to use on the next page)

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Section 2

This section is scored a little differently—follow the instructions on each question and total them at the bottom.

WOMEN ONLY:

_ I am a woman (0=no, 10=yes)
_ my period is heavy and I cannot make it through without disruptive pain (0=no, 1=yes) _ infertility (0=no, 1=yes)
_ multiple miscarriages (0=no, 1=yes)

EVERYONE:

  • _  anemia of any type (0=no, 1=yes)

  • _  osteoporosis or osteopenia (0=no, 1=yes)

  • _  history of chronic viral condition (Epstein Barr, Mono, Herpes, Shingles, Chronic Fatigue Syndrome, Hepatitis, or other chronic viral condition) (0=no, 5=yes)

  • _  a doctor has told me I was too sensitive (0=no, 5=yes)

  • _  members of my immediate family have autoimmune conditions (0=no, 5=one 10=more than one)

    ANSWER ONE OF THE FOLLOWING, IF THEY APPLY TO YOU:

  • _  I have a diagnosis of one autoimmune disease (0=no, 30=yes)

  • _  I have a diagnosis of two autoimmune diseases (0=no, 40=yes, in addition to the previous question)

  • _  I have a diagnosis of three or more autoimmune diseases (0=no, 50=yes, in addition to the previous two questions)

    _ Total for Section 2

    Now you will want to add up the values from section 1 and section 2 to discover your autoimmune status. _ Section 1 total + _ Section 2 total = _ your autoimmune status

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AUTOIMMUNE STATUS SELF-TEST SCORING

1–29 STATUS 1:

It appears your client’s risk for having an autoimmune disease is low, however if some of the symptoms they are experiencing are bothersome they should be encouraged to speak with a doctor to find out if they could be caused by other conditions.

30–59 STATUS 2:

It appears your client’s risk for having an autoimmune disease is average. This is the phase practitioners sometimes refer to as “silent autoimmunity”. This means that there may be antibodies present, but they are not yet experiencing disruptive symptoms. If your client is suffering from autoimmune disease, this is the best time to help them seek diagnosis and take action.

60–99 STATUS 3:

It appears your client’s risk for having an autoimmune disease is high, and it is possible that some of their symptoms could be caused by an autoimmune reaction. Intervention at this status can significantly improve their quality of life.

100+ STATUS 4:

Your client has been diagnosed with an autoimmune disease already, or their combination of health history and current symptoms make diagnosis very likely. It is necessary to for them to assemble a healthcare team (if they don’t already have one), start treatment, and consider changes immediately in order to regain quality of life.

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AUTOIMMUNE WELLNESS MANIFESTO

We will be covering all the details and applying some of the principles of the autoimmune wellness journey together, but this manifesto is a way to boil the process down to a few uncomplicated points. These tenets can serve as guideposts on this journey and help you fight overwhelm or find inspiration on your mission of wellness. Post them on your fridge or tape them to your bathroom mirror to help you keep perspective.

  1. Trust your intuition. You don’t need a guru to navigate this process successfully.

  2. Embrace the template. The Autoimmune Protocol is not one-size-fits-all; it’s a template that

    promotes individuality and self-discovery.

  3. Information is power. Learn enough to be an informed and proactive advocate for your health.

  4. Start simple. Begin with the foundations of diet, sleep, stress-management, movement, and relationships before delving deeper.

  5. Take it slow. Don’t be afraid to make changes in phases–it was the tortoise and not the hare that won the race!

  6. Food is your friend. It provides nourishment to every single cell in your body!

  7. Set yourself up for success. Planning and preparation are the key.

  8. Be a nutrient-seeker. Don’t ignore the foods that accelerate healing and restore health.

  9. Food over supplements. Nutrients are often synergistic and more potent in nature’s packaging.

  10. Don’t diet “harder.” Resist the temptation to further restrict instead of troubleshooting.

  11. Seek help. When necessary, thoughtfully add practitioners to your team that are willing to collaborate, not undermine your authority on you.

  12. Test, don’t guess. Always use testing to reveal root issues if progress is not as expected.

  13. Be skeptical. “Magic bullets” that only the elite can afford are not the solution to our

    healthcare crisis.

  14. Strive for balance. Restoring your health is a worthy pursuit but it is not a religion.

  15. Support is crucial. If your networks aren’t strong enough, explore ways to add to your human connections.

  16. Reframe the negatives. Find areas where your life has been expanded by your experience with illness.

  17. Practice gratitude. Give thought energy to what is good and right in your life.

  18. Eyes on your own journey. The path to wellness is unique for all of us. Resist the urge to compare.

  19. Health before image. Value wellness above numbers on a scale or reflections in a mirror.

  20. Vibrant health is a lifelong journey. Nobody ever regrets investing in their wellness. Enjoy the process of restoring your health!

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GUIDE TO KEEPING A SYMPTOM JOURNAL

Journaling is a tool that everyone can use to track their progress while on a healing journey. The ways of keeping a journal are innumerable—you could use pen and paper, a word or text document on your computer, a spreadsheet, or a app on your smartphone. More important than the method you use to track is the fact that you actually do it in a consistent way, which produces useable data that you and your coach can use to help inform future decisions.

Metrics to track:

  • Energy

  • Pain

  • Bowel movements

  • Exercise

  • Mood

  • Food/beverage intake (see note)

  • Notable symptoms

  • Body measurements

  • Digestion

  • Medications

  • Supplements

  • Stress management

    Tracking tips:

  • Use a scale from 1–10 instead of adjectives (like “energy—7” instead of “I had a good amount of energy today”), making your data more useable. This will also make it quicker for you to track, and the results are easy to compare.

  • In order to avoid overwhelm, only track what is important. Start with a few metrics and build as you get into the habit.

  • Don’t beat yourself up if you get busy and forget a few days. Maintaining the record long-term is useful even if there are some gaps.

  • Use the Bristol Stool Chart, a specific system of tracking bowel movements to assess your eliminations.

    A note about food and weight tracking—don’t obsessively count food intake or weigh yourself every day. When tracking food, describing the foods you ate that day (i.e. Salad with carrots, lettuce, beets, canned salmon and avocado dressing) in enough detail to make connections about diet and symptoms. Even if you would like to lose weight, ditch the scale (that number doesn’t tell us anything about your value!) and rely on weekly body measurements instead.

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FOOD JOURNAL

Write down everything you eat and drink, including all snacks, beverages, water, and any supplements or medications you take. Include approximate amounts (there is no need to measure, but give yourself enough info to make your data useful over time) and times. If you notice any mood or physical changes (i.e. anxiety, headache, bloating, etc.) associated with a meal, snack, or beverage, record it in the right- hand column. An example would be: Breakfast, 7 AM, 1 bowl chicken and mushroom soup, 1 glass lemon water, 15 mg zinc, bloating, mood upbeat. Use a new form for each day of the week.

BREAKFAST (TIME: )

SUPPLEMENTS/MEDICATIONS:

MEAL

BEVERAGE

MOOD/PHYSICAL CHANGES

SNACK (TIME: )

SUPPLEMENTS/MEDICATIONS:

LUNCH (TIME: )

SUPPLEMENTS/MEDICATIONS:

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MEAL

BEVERAGE

MOOD/PHYSICAL CHANGES

SNACK (TIME: )

SUPPLEMENTS/MEDICATIONS:

SNACK (TIME: )

SUPPLEMENTS/MEDICATIONS:

DINNER (TIME: )

SUPPLEMENTS/MEDICATIONS:

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LIFESTYLE JOURNAL

Below is a list of four questions in each of the four lifestyle areas to ask yourself at the end of each day. Use this to check-in with yourself daily, jotting down simple answers. Over time you can see if you are on track in each area, if habits are improving, or if some areas need more focus. Use a new form each day.

DATE (M/D/Y):

Rest

  1. How many hours of sleep did I get last night? 1 / 2 / 3 / 4 / 5 / 6 / 7 / 8 / 9 / 10 / 11 / 12

  2. Did I have trouble falling asleep or staying asleep? Yes / No

  3. Did I feel rested upon waking? Yes / No

  4. What sleep hygiene steps did I take last night?

Breathe

  1. Were my stress-management techniques adequate for today’s stress levels? Yes / No

  2. Was my technology time balanced with screen-free moments of mindfulness? Yes / No

  3. Did I prioritize self-care today (such as bathing, eating, etc.)? Yes / No

  4. What stress-management or self-care activities did I engage in today?

Move

  1. Did I get some movement today, avoiding being too sedentary? Yes / No

  2. Did I feel good moving today or did it cause any pain? Yes/No

  3. After moving, did I feel tired, but happy or was I totally depleted? Yes / No

  4. What did I do to move today, and for how long?

Connect

  1. Did I give time to my special relationships today? Yes / No

  2. Did I engage in human interaction, rather than only connecting virtually? Yes / No

  3. Did I get outside today for at least 15 minutes or more? Yes / No

  4. What things about the natural world or my special relationships did I especially appreciate today?

Did anything else notable happen in these areas that I’d like to document today?

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SYMPTOM JOURNAL

In each of the first four rows record a number between 1 and 10 representing how you felt in that area on that day. Next circle any digestive symptoms experienced on that day, note bowel movement scores per the Bristol Stool Chart, and add any notable symptoms using the list on page 2 to help you. Once a week, also note body measurements per page 2. Use a new form each week.

DATES (M/D/Y–M/D/Y):

ENERGY

1=very low energy 10=very high energy

PAIN

1=very low pain 10=very high pain

STRESS LEVEL

1=very low stress 10=very high stress

MOOD

1=very low mood 10=very high mood

DIGESTION

Belching Bloating Cramping Flatulence Heartburn Nausea

Belching Bloating Cramping Flatulence Heartburn Nausea

Belching Bloating Cramping Flatulence Heartburn Nausea

Belching Bloating Cramping Flatulence Heartburn Nausea

Belching Bloating Cramping Flatulence Heartburn Nausea

Belching Bloating Cramping Flatulence Heartburn Nausea

Belching Bloating Cramping Flatulence Heartburn Nausea

BOWEL MOVEMENTS

BM 1- BM 2- BM 3-

BM 1- BM 2- BM 3-

BM 1- BM 2- BM 3-

BM 1- BM 2- BM 3-

BM 1- BM 2- BM 3-

BM 1- BM 2- BM 3-

BM 1- BM 2- BM 3-

NOTABLE SYMPTOMS

MONDAY

TUESDAY

WEDNESDAY

THURSDAY

FRIDAY

SATURDAY

SUNDAY

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NOTABLE SYMPTOMS:

Acne

Dizzy or lightheaded
Dry hair, skin, or nails
Fatigue (from mild to unable to stay awake) Headache (from mild to migraine)
Hives
Insomnia
Itchy eyes, mouth, ears, or skin
Joint aches or pains
Ligament aches or pains
Low stress tolerance
Muscle aches or pains

Neck aches or pains
Need for caffeine
Phlegm, runny nose, or postnasal drip Pink bumps or spots
Rash
Sinus pressure
Sneezing
Stomach aches or pains
Tendon aches or pains
Unrested after sleep
Other:

Anxiety

Back aches or pains

Breast tenderness

Cough or need to clear throat

Cravings (Fatty)

Cravings (Salty)

Cravings (Sweet)

Cravings for non-food items (like chalk, dirt, or clay)

Depression

Body measurements (1x/week):

Weight: Chest: Waist:

Hips: Thighs:

Calves: Upper Arms:

Were there any notable symptoms that need more explanation this week? If so, describe below:

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BRISTOL STOOL CHART

Use this chart to easily describe the appearance of your stool. It can be helpful to keep a notebook in your bathroom, and write down the date, time, and type of stool. Additional tracking, such as color or size (S, M, L) can be helpful as well.

TYPE 1

Separate hard lumps, hard to pass

TYPE 2

Sausage-shaped but lumpy

TYPE 3

Like a sausage but with cracks on the surface

TYPE 4

Like a sausage or snake, smooth and soft

TYPE 5

Soft blobs with clear-cut edges (passed easily)

TYPE 6

Fluffy pieces with ragged edges, a mushy stool

TYPE 7

Watery, no solid pieces, entirely liquid

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