AUTOIMMUNE Ayesha Rasheed

DISEASES B.Sc (Hons.) HND

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 ROADMAP
Sr. Contents Slide No.
No.
1. Introduction to autoimmune diseases 3-11
2. Common autoimmune diseases 12
1. Diabetes 13-24
2. Rheumatoid arthritis 25-32
3. Multiple Sclerosis 33-37
4. Celiac Disease 38-44
3. Diagnosis of autoimmunity 45-47
4. Treatment options for autoimmune diseases 48-49

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1. INTRODUCTION
‘‘A healthy immune system defends the body
against disease and infection. But if the immune
system malfunctions, it mistakenly recognizes its
own constituent parts as non-self which allows an
immune (abnormal) response against its own cells,
tissues and organs. This phenomenon is known as
autoimmunity.’’

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1. INTRODUCTION CONT..
A defect in any arm of the immune system can trigger autoimmunity.

Cell-mediated
T cells
Acquired
Immune Humoral
system
B cells
Innate
Complement

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 IMMUNE SYSTEM MALFUNCTION
Immune system cells called T lymphocytes (T cells) use special receptors on their
surfaces to identify foreign microbes such as bacteria and viruses. The 'self-attacking' T
cells that escape destruction (by the thymus) may be activated by a trigger. The exact
triggers are unknown, but viral infections and hormones are among the suspects. The T
cells then instruct B lymphocytes (B cells) to make antibodies against the particular
tissue, organ or system. Such antibodies are called 'autoantibodies’. The mechanisms
involve molecular mimicry, abnormal presentation or overproduction of self antigens,
failure to delete auto-reactive lymphocytes etc.

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MAJOR EXAMPLES
• Rheumatoid arthritis (RA) • Coeliac disease

• Diabetes mellitus type 1 (IDDM) • Inflammatory Bowel Disease (IBD)

(Crohn’s disease or ulcerative colitis)
• Addison’s disease
• Pernicious anaemia
• Grave’s disease
• Multiple sclerosis (MS)
• Idiopathic thrombocytopenic purpura
(ITP) • Lupus

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1.A. CAUSES OF AUTOIMMUNITY
The exact causes of autoimmune disorders are not known. The risk factors seem to include:

• Genetics – a predisposition to autoimmune disorders seems to run in families. However,

family members can be affected by different disorders; for example, one person may have
diabetes, while another has rheumatoid arthritis.

• Gene-environment interaction – a family's susceptibility to autoimmune disorders may

be linked to common environmental factors, perhaps working in conjunction with genetic
factors e.g., gene-environment (cigarette smoking) interaction in rheumatoid arthritis (RA).

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1.A. CAUSES CONT..
• Gender – the incidence of autoimmune diseases such as MS, lupus and RA is higher in
women than in men. 

• Sex hormones – Androgens, testosterone and progesterone may protect from

autoimmune diseases; estrogen seem to protect from rheumatoid arthritis but to be
deleterious in lupus.

• Childhood poverty – researchers discovered a link between lower socioeconomic

status in childhood and rheumatoid arthritis in adulthood.

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1.A. CAUSES CONT..
• Diet – vitamin D may be important for preventing immune dysfunction in older
populations; dietary micronutrients could either improve or worsen lupus symptoms.

• Sunlight – exposure to UV rays from sunlight may be connected to the development of

juvenile dermatomyositis, an autoimmune disease associated with muscle weakness and
skin rashes.

• Agricultural chemicals – exposure to some pesticides may play a role in the

development of RA in male farm workers.

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1.A. CAUSES CONT..
• Organic mercury – Methylmercury, even at exposure levels generally considered safe,
may be linked to development of autoantibodies in women of reproductive age. These
antibodies could lead in turn to autoimmune diseases such as IBD, RA and MS.

• Infection – some disorders seem to be triggered or worsened by particular infections.

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1.B.
SYMPTOMS
OF
AUTOIMMUN
E
DISORDERS

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2. COMMON AUTOIMMUNE
DISEASES

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2.1. TYPE-1 DIABETES MELLITUS
(T1DM)
 The disease is characterized by an absolute deficiency of insulin caused by an
autoimmune attack i.e., infiltration of islets of Langerhans with T cells (insulitis) which
leads to gradual depletion of the β-cell population and thus, functional β cells are low to
absent.

 Symptoms involve polyuria (frequent urination), polydipsia (excessive thirst) and

polyphagia (excessive hunger), often triggered by stress or an illness. These are usually
accompanied by fatigue, weight loss, and weakness.

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2.1.A. NATURAL COURSE OF T1DM
I. Initiating event – Exposure to a virus or toxin (environmental factor) may start the
process of β-cell destruction in individuals with a genetic predisposition that allows
the β cells to be recognized as “nonself’’.

II. Slow β-cell destruction – Over a period of years, this autoimmune attack on the β
cells leads to gradual depletion of the β-cell population.

III. Clinical disease – When the insulin secretory capacity falls below a threshold i.e.,
when 80–90% of the β cells have been destroyed, the symptoms suddenly appear.

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2.1.B. DIAGNOSIS OF T1DM
 The diagnosis is confirmed by a glycosylated haemoglobin concentration ≥ 6.5
mg/dl (normal < 5.7). [Note: The rate of formation of HbA1c is proportional to the
average blood glucose concentration over the previous 3 months.]

 The diagnosis can also be confirmed by a Fasting Blood Glucose test (FBG) ≥ 126
mg/dl (normal is 70–99). [Note: A FBG of 100–125 mg/dl is categorized as an impaired
FBG.] Fasting is defined as no caloric intake for at least 8 hours. The diagnosis can also
be made on the basis of a non-fasting (random) blood glucose level greater than 200
mg/dl in an individual with symptoms of hyperglycaemia.

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MAJOR METABOLIC ABNORMALITIES
IN T1DM
Absolute or relative insulin deficiency

Multiple metabolic effects

CHO metabolism Protein metabolism Lipid metabolism

•  Glucose uptake by certain
tissues (adipose tissue &
muscle)
•  Glycogenolysis
•  Gluconeogenesis
• Protein synthesis • Lipolysis
• Tissue protein degradation • Free fatty acids in
plasma
• Production of amino acids
• Hepatic production of
ketone bodies

Hyperglycaemia Ketoacidosis
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INTERTISSUE
RELATIONSHI
P
IN
T1DM

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MECHANISM OF INCREASED HEPATIC
GLUCOSE OUTPUT

Insulin
 Inhibitory effect on glucagon secretion

 Glucagon

 Gluconeogenesis & glycogenolysis

 Plasma glucose

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 MECHANISMS OF DECREASED
PERIPHERAL GLUCOSE UPTAKE
Muscle Adipose tissue

 Insulin  Insulin

 Glucose & amino acid uptake

 Protein breakdown  Glucose uptake

 Plasma glucose  Plasma glucose

 Plasma amino acids

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LONG-TERM COMPLICATIONS

characterized by

Microvascular Macrovascular
complications complications

Stroke Retinopathy
Cardiovascular Nephropathy
diseases Neuropathy

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 2.1.C. TREATMENT OF T1DM
Individuals with type 1 diabetes must rely on exogenous insulin injected subcutaneously
to control the hyperglycaemia and ketoacidosis.

Insulin therapy

Standard Intensive
treatment treatment

Hypoglycaemia
unawareness

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2.1.C. TREATMENT OF T1DM CONT..

I. Standard insulin therapy:

 Standard treatment typically consists of one or two daily injections of recombinant

human insulin.

 Mean blood glucose levels obtained are typically in the 225–275 mg/dl range, with a
haemoglobin A1C (HbA1c) level of 8–9% of the total haemoglobin. [Note: Normal
mean blood glucose is approximately 100 mg/dl, and HbA1c is 6% or less.]

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2.1.C. TREATMENT OF T1DM CONT..
II. Intensive insulin therapy:

 Intensive treatment seeks to more closely normalize blood glucose through more
frequent monitoring and subsequent injections of insulin, typically three or more times a
day.

 Mean blood glucose levels of 150 mg/dl can be achieved, with HbA1c approximately
7% of the total haemoglobin. [Note: Normal mean blood glucose is approximately 100
mg/dl, and HbA1c is 6% or less.]

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 COMPLICATION OF INSULIN
THERAPY
Hypoglycaemia

 Glucagon and epinephrine

 Hepatic production of glucose

as the disease progresses

 Glucagon and epinephrine

secretion

Symptom-free condition known as “hypoglycaemia

unawareness”
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2.2. RHEUMATOID ARTHRITIS
 RA is the most common form of autoimmune arthritis. About
75% of RA patients are women. The disease most often begins
between the ages of 30 and 50. However, RA can start at any
age.

 Its symptoms include joint pain, stiffness, swelling and

decreased movement of the joints. Stiffness for a long time in
the morning is a clue that one may have RA. For instance,
osteoarthritis most often does not cause prolonged morning
stiffness.
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2.2.A DIAGNOSIS OF RHEUMATOID
ARTHRITIS
• Examining blood test results:

Blood tests are run to look for antibodies in the blood that can been seen in RA. If
antibodies are found in people without RA, this is called a false positive result. Blood
tests are also run to look for high levels of inflammation. Abnormal blood tests
commonly seen in RA include: Anemia (a low red blood cell count), Rheumatoid factor
(an antibody, or blood protein, found in about 80% of patients with RA in time, but in as
few as 30% at the start of arthritis)

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2.2.A DIAGNOSIS OF RA CONT..
• Elevated erythrocyte sedimentation rate (a blood test that, in most patients with RA,
confirms the amount of inflammation in the joints)

• Examining the joints and organs

• Reviewing x-ray or ultrasound images

• X-rays can help in detecting RA, but may be normal in early arthritis. MRI and
ultrasound scanning can be done to help confirm or judge the severity of RA.

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2.2.C TREATMENT OF RA
 If a person receives a diagnosis of RA, the doctor may
refer them to a specialist known as a rheumatologist, who
will advise on treatment options. There is currently no cure
for RA, but treatment can help to:

• reduce inflammation to the joints; relieve pain

• minimize any loss of function caused by pain, joint

damage, or deformity

• slow down or prevent damage to the joints

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2.2.C TREATMENT OF RA CONT..
 Treatment options include:

• Medications i.e., Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), corticosteroids

• physical therapy,

• occupational therapy and counseling,

• surgery

 Medications such as NSAIDs and corticosteroids reduce pain and inflammation and
may play a role in slowing down joint damage, but they cannot cure R.A

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2.2.C TREATMENT OF RA CONT..
• Disease-modifying antirheumatic drugs (DMARDs) can slow the progression of the
RA and prevent permanent damage to the joints and other tissues by interfering with the
overactive immune system. A person usually takes a DMARD for life. Examples include
leflunomide, methotrexate, sulfasalazine, minocycline and hydroxychloroquine.

• Tumor necrosis factor-alpha inhibitors (TNF-alpha inhibitors) prevent

inflammation. They can reduce pain, morning stiffness, and swollen or tender joints.
Examples include (Enbrel), infliximab (Remicade) and adalimumab (Humira).

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2.2.C TREATMENT OF RA CONT..

 Occupational therapy

• An occupational therapist can help the individual learn new and effective ways of
carrying out daily tasks. This can minimize stress to painful joints.

• For example, a person with painful fingers might learn to use a specially devised
gripping and grabbing tool.

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2.2.C TREATMENT OF RA CONT..
 If medication and physical therapy do not help, surgeries can be done to repair
damaged joints, correct deformities, reduce pain etc.

 The following procedures are possible:

i. Arthroplasty: In a total joint replacement, the damaged parts are removed and a
metal and plastic prosthesis, or artificial joint is inserted

ii. Tendon repair: loosed or ruptured tendons are restored through surgery

iii. Arthrodesis: a bone or joint is fuse to decrease pain and realign or stabilize the joint.

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2.3 MULTIPLE SCLEROSIS
• Multiple sclerosis (MS) is a potentially disabling disease
of the brain and spinal cord (central nervous system).

• In MS, the immune system attacks the protective sheath

(myelin) that covers nerve fibers and causes
communication problems between your brain and the rest
of your body. A combination of genetics and environmental
factors appears to be responsible for its progression and
can cause permanent damage or deterioration of the nerves.

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2.3.A SYMPTOMS OF MS
 Multiple sclerosis signs and symptoms may differ greatly from person to person and
over the course of the disease depending on the location of affected nerve fibers.

 Symptoms often affect movement, such as Numbness or weakness in one or more

limbs that typically occurs on one side of your body at a time, or the legs and trunk;
Electric-shock sensations that occur with certain neck movements, especially bending
the neck forward; Tremor, lack of coordination or unsteady gait

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2.3.A SYMPTOMS OF MS CONT..
• Partial or complete loss of vision, usually in one eye at a time, often with pain during
eye movement, prolonged double vision.

• Fatigue

• Dizziness

• Tingling or pain in parts of your body

• Problems with sexual, bowel and bladder function

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2.3.B. TREATMENT OF MS
 Corticosteroids, such as oral prednisone and intravenous methylprednisolone, are
prescribed to reduce nerve inflammation.

 Plasma exchange (plasmapheresis), the liquid portion of part of your blood (plasma)
is removed and separated from your blood cells. The blood cells are then mixed with a
protein solution (albumin) and put back into your body.

 Beta interferons, these medications are among the most commonly prescribed
medications to treat MS. They are injected under the skin or into muscle and can reduce
the frequency and severity of relapses.

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2.3.B. TREATMENT OF MS CONT..
 Glatiramer acetate (Copaxone, Glatopa). This medication may help block your
immune system's attack on myelin and must be injected beneath the skin

 Fingolimod (Gilenya)

 Dimethyl fumarate (Tecfidera),

 Teriflunomide (Aubagio),

 Siponimod (Mayzent) etc.

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 2.4 CELIAC DISEASE
 Celiac disease, sometimes called gluten-sensitive enteropathy, is
an immune reaction to eating gluten, a protein found in wheat,
barley and rye. Eating gluten triggers an immune response in small
intestine. Over time, this reaction damages small intestine's lining
and prevents it from absorbing some nutrients (malabsorption).

• The intestinal damage often causes diarrhea, fatigue, weight loss,

bloating and anemia, and can lead to serious complications.

• In children, malabsorption can affect growth and development.

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2.4 GLUTEN CONTAINING FOODS
 A strict, lifelong gluten-free diet is the only way to manage celiac disease. Besides
wheat, foods that contain gluten include:

• Barley • Graham flour

• Durum • Malt

• Farina • Rye

• Spelt (a form of wheat) • Semolina

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2.4.A SYMPTOMS OF CELIAC
DISEASE
Symptoms in Adults Symptoms in Children
Diarrhea Nausea and vomiting
Fatigue Chronic diarrhea
Weight loss Swollen belly
Bloating and gas Constipation
Abdominal pain Gas
Nausea and vomiting Pale, foul-smelling stools
Constipation

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2.4.A SYMPTOMS OF CELIAC
DISEASE CONT..
Digestive Problems in Adults Digestive Problems in Children

Anemia, usually from iron deficiency Failure to thrive for infants

Damage to tooth enamel
Osteoporosis and Osteomalacia
Weight loss
Itchy, blistery skin rash
Anemia
Mouth ulcers Short stature
Headaches and fatigue Delayed puberty

Reduced functioning of the spleen Neurological disabilities

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2.4.B CAUSES OF CELIAC DISEASE
 When the body's immune system overreacts to gluten in
food, the reaction damages the tiny, hair-like projections (villi)
that line the small intestine. Villi absorb vitamins, minerals and
other nutrients from the food you eat. If your villi are damaged,
you can't get enough nutrients, no matter how much you eat.

 Sometimes celiac disease becomes active after surgery,

pregnancy, childbirth, viral infection or severe emotional stress.

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2.4.C COMPLICATIONS OF CELIAC
DISEASE
 Malnutrition
Cancer: People with celiac disease who
 Bone weakening and infertility and don't maintain a gluten-free diet have a
miscarriage (Malabsorption of calcium greater risk of developing several forms
and vitamin D) of cancer

 Lactose intolerance: Damage to your Nervous system problems: Some

small intestine might cause you abdominal people with celiac disease can develop
pain and diarrhea after eating or drinking problems such as seizures
dairy products that contain lactose.
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2.4.D TREATMENT OF CELIAC
DISEASE
 A dietitian who works with people with celiac disease can help you plan a healthy
gluten-free diet. Even trace amounts of gluten in your diet can be damaging, even if they
don't cause signs or symptoms. Removing gluten from your diet will gradually reduce
inflammation in your small intestine, causing you to feel better and eventually heal.
Children tend to heal more quickly than adults.

 If anemia or nutritional deficiencies are severe, supplements are recommended i.e.

vitamin B complex, zinc etc.

 Steroids that control inflammation while the intestine heals.

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3. DIAGNOSIS OF AUTOIMMUNITY
 Complete blood count (CBC), a collection of tests measuring the size, number
and maturity of different blood cells in a specific amount of blood. Two important
tests are: white blood cell count (WBC), which measures the number of white blood
cells present, and haematocrit, which measures the number of red blood cells
present.

 Erythrocyte sedimentation rate (ESR or sed. rate), which measures how

quickly red blood cells fall to the bottom of a test tube. If the cells to clump together
and fall more rapidly than normal, it can signal inflammation in the body.

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3. DIAGNOSIS CONT..
 Antinuclear antibody (ANA), which can detect certain abnormal proteins called
antinuclear antibodies that the immune system makes when attacking the body's own
tissues.

 Rheumatoid factor (RF), which, like ANA, can detect an abnormal protein that the
immune system makes when attacking the body.

 Complement, which measures the blood's level of complement, a group of proteins

that are part of the immune system. Low levels of complement may indicate an
autoimmune problem.

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3. DIAGNOSIS CONT..
 C-reactive protein (CRP), which measures the amount of a special protein made in
the liver. CRP levels tend to shoot upward when there's severe inflammation like the
kind seen in autoimmune diseases somewhere in the body.

 Immunoglobulins Blood Test, which checks the amount of certain antibodies called

immunoglobulins in your body. If your immunoglobulin level is high, it might be caused
by an autoimmune disorder that makes your immune system overreact, such
as rheumatoid arthritis, lupus, or celiac disease.

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4. TREATMENT OPTIONS FOR
AUTOIMMUNE DISEASES
Treatments can’t cure autoimmune diseases, but they can control the overactive immune
response and bring down inflammation or at least reduce pain and inflammation. Drugs
used to treat these conditions include:

• Nonsteroidal anti-inflammatory drugs (NSAIDs) – to reduce inflammation and pain

such as ibuprofen (Motrin, Advil) and naproxen (Naprosyn)

• Pain-killing medication – such as paracetamol and codeine

• Immunosuppressant drugs – to inhibit the activity of the immune system

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4. TREATMENT OPTIONS CONT..
• Corticosteroids – to reduce inflammation, such as prednisone and cortisone

• Treatment for the deficiency – for example, insulin injections in the case of diabetes

• Cytotoxic drugs – to reduce disease activity in skin or internal organs i.e., contain
chemicals which are toxic to cells, preventing their replication or growth

• Surgery – for example, to treat bowel blockage in the case of Crohn's disease

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