AUTOIMMUNE DISEASE

DEFINITION AND INTRODUCTION

• Autoimmune diseases is a group of disorders in which tissue injury is
caused by humoral (by auto-antibodies) or cell mediated immune
response (by auto-reactive T cells) to self antigens tissue.

• Normally the immune system does not attack the self. However, there is
a large group of autoimmune diseases in which the immune system
does attack self cells.

• The attack can be directed either against a very specific tissue or to a

large no. of tissues.

• An autoimmune disease is a condition in which your immune system

mistakenly attacks your body.

• The immune system normally guards against germs like bacteria and
viruses. When it senses these foreign invaders, it sends out an army of
fighter cells to attack them.

• Normally, the immune system can tell the difference between foreign
cells and your own cells.

• In an autoimmune disease, the immune system mistakes part of your

body — like your joints or skin — as foreign. It releases proteins called
auto-antibodies that attack healthy cells.
 • Some autoimmune diseases target only one organ. Type 1 diabetes
damages the pancreas. Other diseases, like lupus, affect the whole body.

AUTO IMMUNITY

• Auto or self antigens

- Antigens present in ones own cells .

- Altered by the action of bacteria , viruses, chemicals, or drugs as a non-

self

• Auto antibody
- Altered cell ( Auto Ag ) – elicits the production of Antibody .

• Auto Immunity ( misnomer , alternative = auto

allergy )
- Immune response of auto Ab against self Ag

- Humoral or cell mediated immune response against the constitute’s of

the body’s own tissues.

- There are more than 80 different kinds of diseases caused by

autoimmunity.
AUTOIMMUNITY VS. AUTOIMMUNE
DISEASES
Autoimmunity does not necessarily mean autoimmune disease. For example,
the body may produce antibodies against itself (autoantibodies) that are
involved in cleaning up debris after an infection. With autoimmune disease,
the reaction causes inflammation and tissue damage.

There is a wide range of autoimmune diseases that together may affect tissues
in nearly any region of the body. These conditions fall along a spectrum, but
can be broken down into organ-specific diseases (those that affect primarily
one organ) and generalized or systemic diseases, which affect many types of
tissues or organs. Some of these generalized conditions may affect blood
vessels, endocrine glands, the skin, joints, or muscles.

CAUSES OF AUTOIMMUNE DISEASES

1. Sequestered or Hidden antigens
• Ag in the secluded places – are not accessible to the immune system.
• E.g. Lens Ag, Sperm Ag & Thyroglubulin.

2. Neo antigens
• Altered or modified antigens- by physical (irradiation), (chemical (drugs)
or microbial agents intracellular viruses).

3. Cessation of Tolerance
 • It may result when tolerance to the self –Ag is abrogated.

4. Cross reacting Antigens

• A foreign Ag which resembles self a 2nd Ag.
• Many species share organ specific Ags.
• E.g. Ag of Human brain & Ag of sheep brain, Streptococcal M protein &
Heart muscles, Nephritogenic strains of Streptococcai Ags & Renal
glomeruli shares similar epiotes.

5. Loss of Immunoregulation
• Loss of Self tolerance – caused by over activity or lowered activity of T
and B- cells.

FACTORS INCREASING RISK

• Cigaratte smoking : RA+ , SLE ( Varies per country ).
• Atopic Allergies
• Psychosocial Stress : 5 years period ( relationship , job,
financial) (RA)

• Use of Private well-water

• Hair dye
• Hep B vaccination :(SLE )
• EBV, Herpes Viral infections : ( SLE)
 • Pneumonia: ( RA)
• Pre-eclampsia: ( RA+SLE)
• Cystaline Silica Exposure : ( GENERAL )
• Drugs and contaminants: Canola oil , Tryptophan ,
procainamide , interferon .

• Xenoestrogen : exposure ( BPA ,DDT ,TTCD- Tetrachlorodioxin )

FACTORS DECREASING RISK

• Breast Fed : protects against RA and SLE
• Past Urinary Tract Infections : Protects against RA .
• Past Rubella Infection ( German Measles ) :
Protects against RA .

COMMON AUTOIMMUNE DISEASES

• Rheumatoid Arthritis
• Systemic lupus
• Hyper and Hypo Thyroid
• Multiple sclerosis
• Pernicious and hemolytic anemias
• Diabetes Mellitus
• Vitiligo
• Psoriasis
 • Chrone’s disease
• Ulcerative Colitis
• Celiac Disease
• Possible Autoimmune Components
• Fibromyalgia
• Lyme’s Disease

CLASSIFICATION OF AUTOIMMUNE
DISEASES
Broadly classified into 3 groups

1. haemolytic autoimmune diseases

2. Localised

3. Systemic autoimmune diseases

1. Haemolytic Autoimmune Diseases

- Clinical disorder due to destructions of blood components . Auto Ab are
formed against one’s own RBCs , Platelets or leucocytes .

- E.g. Haemolytic anaemia , Leucopenia , Thrombocytopenia , etc.

2. Localised autoimmune diseases or Organ specific

autoimmune diseases
- A particular organ is affected due to Abs .
- For example :

• Thyroiditis ( attacks the thyroid )

• Multiple sclerosis ( attacks myelin coating of nerve axons )
• Myasthenia gravis ( attacks nerve – muscle junction )
• Juvenile diabetes or Type I D M ( attacks insulin – producing cells )

3. Systemic autoimmune diseases or Non – organ

specific autoimmune diseases
- Immune complexes accumulate in many tissues and cause inflammation and
damage .

- Affects many organs or the whole body .

- For example :

• Systemic Lupus Erythematosus ( anti – nuclear Ab. ) : harms kidneys,

heart, brain , lungs, skin …
• Rheumatoid Arthritis ( anti IgG Antibodies ) : Joints , hearts , lungs,
nervous system …
• Rheumatic fever : cross – reaction between antibodies to streptococcus
and auto – antibodies .

14 COMMON AUTOIMMUNE DISEASES

There are more than 80 different autoimmune diseases . Here are 14 of the
most common ones.

1. Type 1 diabetes
The pancreas produces the hormone insulin, which helps regulate blood sugar
levels. In type 1 diabetes, the immune system attacks and destroys insulin-
producing cells in the pancreas.

High blood sugar can damage blood vessels, as well as organs like the heart,
kidneys, eyes, and nerves.

2. Rheumatoid arthritis (RA)

In rheumatoid arthritis (RA), the immune system attacks the joints. This attack
causes redness, warmth, soreness, and stiffness in the joints.

Unlike osteoarthritis, which affects people as they get older, RA can start as
early as your 30s .
3. Psoriasis/psoriatic arthritis
Skin cells normally grow and then shed when they’re no longer
needed. Psoriasis causes skin cells to multiply too quickly. The extra cells build
up and form red, scaly patches called scales or plaques on the skin.

About 30 percent of people with psoriasis also develop swelling, stiffness, and
pain in their joints . This form of the disease is called psoriatic arthritis.

4. Multiple sclerosis
Multiple sclerosis (MS) damages the myelin sheath — the protective coating
that surrounds nerve cells. Damage to the myelin sheath affects the
transmission of messages between your brain and body.

This damage can lead to symptoms like numbness, weakness, balance issues,
and trouble walking. The disease comes in several forms, which progress at
different rates. About 50 percent of people with MS need help walking within
15 years after getting the disease .

5. Systemic lupus erythematosus (lupus)

Although doctors in the 1800s first described lupus as a skin disease because
of the rash it produces, it actually affects many organs, including the joints,
kidneys, brain, and heart .

Joint pain, fatigue, and rashes are among the most common symptoms.
CHARACTERISTICS OF SLE :

- Appearance of blood red spots over the bridge of nose and cheeks . The
lesions take the shape of a butterfly .
- Coonective tissue of the skin , kidney, heart. Speel & blood vessels are
severly damaged resulting in joint pain , fever & anaemia.
- Glomerulonephritis due to deposition of immune complex in the
glomerulus region .
- It is a systemic disease affecting the whole body.

6. Inflammatory bowel disease

Inflammatory bowel disease (IBD) is a term used to describe conditions that
cause inflammation in the lining of the intestines. Each type of IBD affects a
different part of the GI tract.

• Crohn’s disease can inflame any part of the GI tract, from the mouth to the
anus.
• Ulcerative colitis affects only the lining of the large intestine (colon) and
rectum.

7. Addison’s disease
Addison’s disease affects the adrenal glands, which produce the hormones
cortisol and aldosterone. Having too little of these hormones can affect the
way the body uses and stores carbohydrates and sugar.

Symptoms include weakness, fatigue, weight loss, and low blood sugar.

8. Graves’ disease
Graves’ disease attacks the thyroid gland in the neck, causing it to produce
too much of its hormones. Thyroid hormones control the body’s energy
usage, or metabolism.

Having too much of these hormones revs up your body’s activities, causing
symptoms like nervousness, a fast heartbeat, heat intolerance, and weight loss.

One common symptom of this disease is bulging eyes, called exophthalmos. It

affects up to 50 percent of people with Graves’ disease .
9. Sjögren’s syndrome
This condition attacks the joints, as well as glands that provide lubrication to
the eyes and mouth. The hallmark symptoms of Sjögren’s syndromeare joint
pain, dry eyes, and dry mouth.

10. Hashimoto’s thyroiditis

In Hashimoto’s thyroiditis, thyroid hormone production slows. Symptoms
include weight gain, sensitivity to cold, fatigue, hair loss, and swelling of the
thyroid (goiter).
11. Myasthenia gravis
Myasthenia gravis affects nerves that help the brain control the muscles. When
these nerves are impaired, signals can’t direct the muscles to move.

The most common symptom is muscle weakness that gets worse with activity
and improves with rest. Often muscles that control swallowing and facial
movements are involved.

12. Vasculitis
Vasculitis happens when the immune system attacks blood vessels. The
inflammation that results narrows the arteries and veins, allowing less blood to
flow through them.

13. Pernicious anemia

This condition affects a protein called intrinsic factor that helps the intestines
absorb vitamin B-12 from food. Without this vitamin, the body can’t make
enough red blood cells.

Pernicious anemia is more common in older adults. It affects 0.1 percent of

people in general, but nearly 2 percent of people over age 60 .

14. Celiac disease

People with celiac disease can’t eat foods containing gluten — a protein found
in wheat, rye, and other grain products. When gluten is in the intestine, the
immune system attacks it and causes inflammation.
Celiac disease affects about 1 percent of people in the United States . A larger
number of people have gluten sensitivity, which isn’t an autoimmune disease,
but can have similar symptoms like diarrhea and abdominal pain.

WHY DOES IMMUNE SYSTEM ATTACK THE

BODY ?
Doctors don’t know what causes the immune system misfire. Yet some people
are more likely to get an autoimmune disease than others.

Women get autoimmune diseases at a rate of about 2 to 1 compared to men

— 6.4 percent of women vs. 2.7 percent of men . Often the disease starts
during a woman’s childbearing years (ages 14 to 44).

Some autoimmune diseases are more common in certain ethnic groups. For
example, lupus affects more African-American and Hispanic people than
Caucasians.

Certain autoimmune diseases, like multiple sclerosis and lupus, run in families.
Not every family member will necessarily have the same disease, but they
inherit a susceptibility to an autoimmune condition.

Because the incidence of autoimmune diseases is rising, researchers suspect

environmental factors like infections and exposures to chemicals or solvents
might also be involved .

A “Western” diet is another suspected trigger. Eating high-fat, high-sugar, and

highly processed foods is linked to inflammation, which might set off an
immune response. However, this hasn’t been proven .
Another theory is called the hygiene hypothesis. Because of vaccines and
antiseptics, children today aren’t exposed to as many germs as they were in
the past. The lack of exposure could make their immune system overreact to
harmless substance

AUTOIMMUNE DISEASE SYMPTOMS

The early symptoms of many autoimmune diseases are very similar, such as:

• fatigue
• achy muscles
• swelling and redness
• low-grade fever
• trouble concentrating
• numbness and tingling in the hands and feet
• hair loss
• skin rashes

Individual diseases can also have their own unique symptoms. For example,
type 1 diabetes causes extreme thirst, weight loss, and fatigue. IBD causes
belly pain, bloating, and diarrhea.

With autoimmune diseases like psoriasis or RA, symptoms come and go.
Periods of symptoms are called flare-ups. Periods when the symptoms go
away are called remissions.

SPECIFIC SYMPTOMS
Specific symptoms will vary depending on the underlying disorder and may
include:
 • Joint symptoms, such as redness, pain, and joint swelling that is more
severe than would be expected with osteoarthritis
• Skin rashes, such as a "butterfly rash" on the face with lupus
• Vasculitis, inflammation of blood vessels that can lead to damage
wherever blood vessels are affected (e.g. aneurysms)

Many autoimmune conditions are suspected based on a

particular combination of symptoms, although two people can have the
same diagnosis and very different symptoms.

For example, scleroderma (systemic sclerosis) is characterized by something

called CREST syndrome, which stands for the combination of calcinosis (build-
up of calcium), Raynaud's syndrome (a condition in which the hands become
cold and often blue or white upon exposure to cold temperatures),
esophageal dysfunction, sclerodactyly (a condition in which the fingers
resemble sausages), and telangiectasias (abnormally dilated capillaries that
cause the appearance of "spider veins").

SYMPTOMS OF AUTOIMMUNE CONDITIONS

Co-Occurence
It's not uncommon for people who have one autoimmune disease to develop
another. This can be related to a genetic predisposition or a common trigger.

Overall, around 25 percent of people who have one autoimmune disease have
a tendency to develop another.

An example is a combination of rheumatoid arthritis with autoimmune

thyroiditis, or the combination of celiac disease with type I diabetes,
autoimmune liver disease, or rheumatoid arthritis.

The term multiple autoimmune syndrome is used to describe people who

have three or more autoimmune diseases. There are different types of this
syndrome, but frequently one of the three conditions is skin related (such as
alopecia areata or vitiligo).
ETIOLOGY AND PATHOLOGY

1. Thymus Dysfunction : Self reacting lymphoid cells should be

negatively selected if they are sensitive to self antigens . They should undergo
apoptosis ( programmed cell death ). – Called Failure of Clonal Deletion

2. Fewer Suppressor T – Cell : Failure to regulate immune

responses . Some patients have fewer of these cells .

3. Abnormal function of T helper cells : Alterations in

cytokine production .

4. Xenoestrogens : It may result in suppression of cell mediated

immunity and stimulation of humeral immunity .

WHEN TO SEE A DOCTOR

See a doctor if you have symptoms of an autoimmune disease. You might
need to visit a specialist, depending on the type of disease you have.

• Rheumatologists treat joint diseases like rheumatoid arthritis and Sjögren’s

syndrome.
• Gastroenterologists treat diseases of the GI tract, such as celiac and
Crohn’s disease.
• Endocrinologists treat conditions of the glands, including Graves’ and
Addison’s disease.
• Dermatologists treat skin conditions such as psoriasis.

TESTS THAT DIAGNOSE AUTOIMMUNE

DISEASES
No single test can diagnose most autoimmune diseases. Your doctor will use a
combination of tests and an assessment of your symptoms to diagnose you.

The antinuclear antibody test (ANA) is often the first test that doctors use when
symptoms suggest an autoimmune disease. A positive test means you likely
have one of these diseases, but it won’t confirm exactly which one you have.

Other tests look for specific autoantibodies produced in certain autoimmune

diseases. Your doctor might also do tests to check for the inflammation these
diseases produce in the body.

Most Important General Blood Tests

• ESR and CRP

- These measure inflammation in the body . The numbers rise as tissue

destruction becomes more active .

- Can be used to monitor or the condition and assess the success of

treatment .
GENERAL COMPLICATIONS
• Disability due to impaired tissue function

• Complications of immune suppression secondary to drugs : increased

incidence of infections and cancers .

CAUSES AND RISK FACTORS

There are a number of factors that are thought to underlie the development of
autoimmune diseases as well as factors that are associated with an elevated
risk.

Possible causes of autoimmune disease and/or flare-ups include:

• Infectious diseases: It's thought that autoimmunity may occur when a

component of a virus or bacteria resembles proteins in the body, or
instead, by the infection upregulating the immune system. Some specific
microorganisms linked with autoimmune disease include: the Epstein-
Barr virus, cytomegalovirus (CMV), and group A Streptococcus.
• Environmental factors: Lack of sunlight, vitamin D deficiency, chemical
exposure, and other environmental factors have been linked to different
types of autoimmune diseases. A number of studies have also linked a
more sterile environment (fewer pets, cleaner homes, etc.) with the
development of some autoimmune conditions. The theory behind the
"hygiene hypothesis" is that as people are exposed to fewer antigens
(such as dust mites, animal hair, etc.), an overactive immune system
attacks itself.
• Lifestyle: Smoking appears to triple the risk of developing rheumatoid
arthritis and has also been linked with other autoimmune conditions
such as Grave's disease and MS. Obesity is considered a "pro-
inflammatory" state that may account for its role as a risk factor. The
 Western diet (high fat, high sugar, high protein, high salt), in general, is
thought to possibly promote the development of autoimmune diseases.

• Gut bacteria: More and more, research is pointing to a connection

between the bacteria that live in a person's digestive tract (gut flora) and
a number of health conditions, including autoimmune diseases.
• Genetics: Several autoimmune diseases appear to run in families to
varying degrees, with research in progress looking at specific genes.

Risk factors vary depending on the particular condition, but include:

• Sex: Many autoimmune conditions are more common in women. In

addition, hormonal factors can play a role in flare-ups of many of these
conditions.
• Age: Many autoimmune conditions first appear during the childbearing
years.
• Weight: Some autoimmune conditions are more common in people
who are overweight, while others are more common in people who have
a history of eating disorders.
• Ethnicity: Different conditions vary, with type I diabetes being more
common in white people, and severe autoimmune conditions being
more prevalent in African-American, Hispanic, and Native-American
women.
• Geography: Some autoimmune diseases such as multiple sclerosis,
inflammatory bowel disease, and type I diabetes are more common in
northern latitudes, especially the pacific northwest (geographical
differences could, in turn, be linked with vitamin D exposure (there is an
inverse relationship between UV exposure and MS) or ethnicity (such as
Scandinavian heritage).
• Smoking: Tobacco use is associated with an increased risk of many of
these conditions.

• Medications: Some medications may increase risk of certain conditions,

such as is the case with procainamide and lupus.
HOW ARE AUTOIMMUNE DISEASES
TREATED ?
Treatments can’t cure autoimmune diseases, but they can control the
overactive immune response and bring down inflammation. Drugs used to
treat these conditions include:

• nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Motrin,

Advil) and naproxen ( Naprosyn )
• immune-suppressing drugs

Treatments are also available to relieve symptoms like pain, swelling, fatigue,
and skin rashes.

Eating a well-balanced diet and getting regular exercise can also help you feel
better.

BOTTOM LINE: The main treatment for autoimmune diseases is with

medications that bring down inflammation and calm the overactive immune
response. Treatments can also help relieve symptoms.

DIAGNOSIS
The diagnosis of an autoimmune disease can take time and sometimes several
opinions. In fact, and unfortunately, the average person spends four and a half
years (seeing at least four doctors) before a diagnosis is made.
Where to Start
It's recommended that people begin with a specialist who deals with their
most prominent symptom, such as seeing a rheumatologist if joint symptoms
are predominant. Additional specialists may need to be consulted thereafter.

The diagnostic process begins with a careful history, though this can be
frustrating since many people have seemingly unrelated symptoms. A physical
exam can sometimes suggest an autoimmune condition based on joint
swelling, characteristic rashes, and more, but further testing is most often
needed. There isn't one single test that can diagnose autoimmune diseases
conclusively (with rare exceptions such as with type I diabetes), and evaluation
usually includes a number of tests including:

• Erythrocyte sedimentation rate (ESR or sed rate) test

• C-reactive protein (CSR) test
• A complete blood count (CBC)
• A comprehensive metabolic panel
• Antinuclear antibody (ANA) test: Antinuclear antibodies are
autoantibodies that attack structures in the nucleus of cells. Different
patterns on the ANA are correlated with different diseases.
• Rheumatoid factor (RF) test
• Thyroid peroxidase antibodies test

There are many other tests that may be recommended depending on the
condition that is suspected.

Imaging tests may be used when evaluating specific symptoms related to

autoimmune conditions, such as X-rays of joints that are swollen or an
echocardiogram (ultrasound of the heart) if a pericardial effusion is suspected.

• Confirmed by detecting the auto Ab in the serum of the patients.

• Autoantibodies are demonstrated by immunoflurescent Ab test ,
haemagglutination , complement fixation , immunodiffusion ,
Radioimmuno assay , etc.
TREATMENT
The treatments for autoimmune disease vary with the particular disease.

In some cases, the condition may be curable, but for most, remission or
control of the disease is the primary goal.

For many of these conditions, the course is unpredictable, and treatments may
change over time.

• Some autoimmune diseases are treated with medications that alleviate

specific symptoms.
• Haemolytic anaemia: treated with vit B12.
• Throtoxicosis : treated with antithyroid drugs.
• Myasthenia Gravis : treated with choline esterase inhibitors.
• Rhemotoid Arthritis : anti-inflammatory drugs .
• Lupes Erythematosus : treated with immono suppressive or antimitiotic
drugs such as Corticosteoid , cyclophosphamide , and azothioprine.

In general, treatment can be thought of as consisting of:

• Managing symptoms: For example, non-steroidal anti-inflammatory

medications to control joint pain.
• Replacement: For conditions such as type I diabetes or autoimmune
hypothyroidism, insulin or thyroid hormone are given.
• Controlling inflammation: Medications such as corticosteroids and
tumor necrosis factor inhibitors (biologic drugs) are needed to control
inflammation related to many autoimmune conditions
• Preventing complications: Careful blood sugar control is needed in
people with type I diabetes to reduce complications, whereas early and
aggressive treatment is needed with rheumatoid arthritis to prevent
joint deformity.

Clinical trials are also in progress looking for newer, better ways to manage
these conditions.
THE BOTTOM
More than 80 different autoimmune diseases exist. Often their symptoms
overlap, making them hard to diagnose.

Autoimmune diseases are more common in women, and they often run in
families.

Blood tests that look for autoantibodies can help doctors diagnose these
conditions. Treatments include medicines to calm the overactive immune
response and bring down inflammation in the body.

SUMMARY
• Autoimmune diseases and conditions exist when the body produces
abnormal cells , which attack the body , itself.

• Most autoimmune diseases strike women more often than men.

• The causes of autoimmune diseases are not known but some

autoimmune diseases seem to run in families.

• Strike any part of the body , symptoms vary widely and diagnosis and
treatment are often difficult.

• Medical sciences is striving to design therapies that prevent

autoimmune diseases.