Topic 3 Autoimmunity
Part 6 Diabetes
Part 7 Other Diseases
Terry Kotrla, MS, MT(ASCP)BB
Insulin Dependent Diabetes Mellitus
(IDDM)
 Autoimmune process causes destruction of cells in the
pancreas resulting in insufficient insulin production.
 Occurs before age 20, peak onset between 10 and 14 years.
 Inherited susceptibility.
 Environmental influences include possibility of viral
infections.
Complications of Diabetes
 Diabetes is the seventh leading cause of death in the
United States.
 Leading cause of new blindness in people 20-74 years of
age.
 Ten to twenty-one percent of all people with diabetes
develop kidney disease.
 People with diabetes are 2-4 times more likely to have
heart disease.
 About 60%-70% of people with diabetes have mild to
severe forms of diabetic nerve damage, which, in severe
forms, can lead to lower limb amputations.
Laboratory Testing
 The American Diabetes Association (ADA) recommendations for
diagnosing diabetes state that patients be told they have diabetes if
any of the criteria below applies:
 Fasting plasma glucose is above 126 mg/dl;
 Diabetes symptoms exist and casual plasma glucose is equal to or above 200
mg/dl; or
 Plasma glucose is equal to or above 200 mg/dl during an oral glucose
tolerance test.
 The ADA now also recommends that all individuals age 45 and
above be tested for diabetes, and if the test is normal, they should
be re-tested every three years.
 If genetic predisposition is suspected perform testing to detect
antibodies to pancreatic islet cells.
 Antibodies to insulin detected by RIA or ELISA methods.
Indications for Laboratory Testing
 Testing should be conducted at earlier ages and carried out more
frequently in individuals who are any of the following:
 obese;
 have a first degree relative with diabetes;
 are members of a high-risk ethnic population (African-American, Hispanic,
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Native American, Asian);
have delivered a baby weighing more than 9 pounds;
have had gestational diabetes;
are hypertensive;
have HDL cholesterol levels equal to or less than 35 mg/dl or triglyceride
levels equal to or greater than 250 mg/dl;
or who, on previous testing had impaired glucose tolerance or impaired
fasting glucose.
Treatment
 Injected insulin.
 Immunosuppressive drugs for newly diagnosed patients.
Multiple Sclerosis
 Multiple sclerosis (MS) is a chronic, potentially debilitating disease
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that affects the brain and spinal cord (central nervous system).
Destruction of myelin sheath of axons results in formation of
lesions (plaques) in white matter of brain and spinal cord.
Causes inflammation and injury to the sheath and ultimately to the
nerves.
The result may be multiple areas of scarring (sclerosis).
Cause may include genetic and environmental factors.
Most often seen between ages of 20 and 50.
Multiple Sclerosis
Multiple Sclerosis
 Because the myelin is damaged, messages moving along the
nerve are transmitted more slowly or not at all which slows
or blocks muscle coordination, visual sensation and other
nerve signals.
Damage Caused by MS
 Without the protective coating, nerve cells have
difficulty doing their job and sending signals.
 The damage that MS causes can affect:
 Eyes have thousands of nerve fibers to carry visual information
from the retina to the brain, as well as nerve cells controlling
the eye's muscles
 Muscle coordination and strength, because nerve fibers have
direct control of all muscles
 Speech, which is controlled by muscles in the throat, mouth and
tongue
 Bladder and bowel control
Multiple Sclerosis
 MS is a disease that treats each patient differently.
 Approximately 15 percent of patients experience severe
problems that can totally disable them.
 MS generally is not fatal, and most MS patients live a normal life
span.
 MS affects as many as 300,000 Americans.
 There is no cure for MS, but it is treatable.
Diagnosis
 The basic guideline for diagnosing MS relies on two
criteria:
 Must have been two attacks at least one month apart. An attack,
also known as an exacerbation, flare, or relapse, is a sudden
appearance of or worsening of an MS symptom or symptoms
which lasts at least 24 hours.
 There must be more than one area of damage to central nervous
system myelin—the sheath that surrounds and protects nerve
fibers. The damage to myelin must have occurred at more than
one point in time and not have been caused by any other disease
that can cause demyelination or similar neurologic symptoms.
Laboratory Diagnosis
 Cerebrospinal fluid (CSF) is tested for levels of certain
immune system proteins and for the presence of
oligoclonal bands.
 The bands indicate an abnormal autoimmune response
within the central nervous system, meaning the body is
producing an immune response against itself.
 Oligoclonal bands are found in the spinal fluid of about
90-95% of people with MS, but since they are present in
other diseases as well, they cannot be relied on as
positive proof of MS.
 May take years to develop.
CSF Analysis
Treatment
 The treatment of MS focuses mainly on decreasing the rate
and severity of relapse, reducing the number of MS lesions,
delaying the progression of the disease, and providing
symptomatic relief for the patient.
 Several different drugs have been developed to treat the
symptoms of MS.
 Drug treatment depends on the stage of the disease as well as
other factors.
Myasthenia Gravis
 A chronic autoimmune neuromuscular disease characterized
by varying degrees of weakness of the skeletal (voluntary)
muscles of the body.
 It is the most common primary disorder of neuromuscular
transmission
Symptoms
 Facial weakness,
 Difficulty chewing and swallowing,
 Inability to maintain support of trunk, neck or head.
Myasthenia Gravis
 Antibody mediated damage to acetylcholine receptors in skeletal
muscles leading toprogressive muscle weakness.
 Acetylcholine released from nerve endings to generate muscle
contraction.
 Antibody combines with receptor site, blocking acetylcholine
binding.
 Receptors destroyed by action of antibody and complement.
Myasthenia Gravis
Myasthenia Gravis
Laboratory Testing
 Autoantibodies to the Acetylcholine receptor (AChRAb)
can be detected in 80-90% of patients with myasthenia
gravis.
 The assay measures antibodies that precipitate solublized
muscle AChR that has been complexed with radiolabeled
alpha- bungarotoxin (αBTX).
 Antibodies that bind to the receptor regions that are not
sterically blocked by the αBTX are detected.
Goodpasture’s Syndrome
 An uncommon and life-threatening hypersensitivity disorder
believed to be an autoimmune process related to antibody
formation in the body.
 Goodpasture's syndrome is characterized by renal (kidney)
disease and lung hemorrhage.
Goodpasture’s Syndrome
 Antibodies react with antigens in the glomerular basement
membrane of the kidney, results in severe necrosis.
 Antigen in kidney is similar to antigen found in lungs,
resulting in antibody reacting with lung tissue resulting in
pulmonary hemorrhage.
 Specific anti-basement antibodies can be demonstrated.
Symptoms
 Symptoms include:
 foamy,
 bloody, or dark colored urine,
 decreased urine output,
 cough with bloody sputum,
 difficulty breathing after exertion,
 weakness,
 fatigue,
 nausea or vomiting,
 weight loss,
 nonspecific chest pain
 and/or pale skin
Diagnosis
Complete blood count (CBC)
Blood urea nitrogen (BUN) and creatinine levels
Urinalysis will be done to check for damage to the kidneys.
Sputum test to look for specific antibodies.
Chest x ray to assess the amount of fluid in the lung tissues.
Lung needle biopsy and a kidney biopsy will show immune
system deposits.
 Kidney biopsy can also show the presence of the harmful
antibodies that attack the lungs and kidneys
 Antiglomerular basement membrane (anti-GBM) antibody
Enzyme immunoassay (EIA)
 Antibodies to Neutrophil Cytoplasmic Antigens (ANCA)
identified by immunofluorescence
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Treatment
 Corticosteroids
 Plasmapheresis
 Dialysis
Sjogren's Syndrome
 Sjogren's syndrome is an autoimmune disease,
characterized by the abnormal production of extra
antibodies in the blood that are directed against various
tissues of the body.
 This particular autoimmune illness is caused by
inflammation in the glands of the body.
 Inflammation of the glands that produce tears (lacrimal
glands) leads to decreased water production for tears and
eye dryness.
 Inflammation of the glands that produce the saliva in the
mouth (salivary glands, including the parotid glands)
leads to mouth dryness.
Sjogren’s Syndrome
 Chronic autoimmune disorder in which immune cells
attack and destroy the glands that produce tears and
saliva.
 The hallmark symptoms of the disorder are dry mouth
and dry eyes.
 Most often occurs secondary to RA, SLE or other
autoimmune disorders
 Dry eyes and mouth due to damage to secretory ducts.
 90% of cases found in women.
Laboratory Test
 ANA and RF positive
Treatment
 Nonsteroidal anti-inflammatory drugs (NSAIDs), such as
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aspirin and ibuprofen
Corticosteroids
Saliva substitutes
Artificial tears or eye drops
Cyclosporine A (Restasis) eye drops
Scleroderma
 From the Greek words for 'hard' and 'skin' - a rare, chronic
disease characterized by excessive deposits of collagen.
 Causes skin thickening and tightening, and can involve
fibrosis and other types of damage to internal body organs.
 This condition, thought to be an autoimmune disease, affects
both adults and children, most commonly adult women.
 Typically the skin appears reddish or scaly in appearance.
Blood vessels may also be more visible.
 Where large areas are affected, fat and muscle wastage will
weaken limbs and affect appearance.
Scleroderma
 CREST syndrome
 Calcinosis
 Raynaud’s Phenomena
 Esophageal dysmotility
 Sclerodactyly
 Telangiectases
Calcinosis
 The buildup of calcium deposits in the tissues.
 It may occur under the skin of the fingers, arms, feet, and
knees, causing pain and infection if the calcium deposits
pierce the surface of the skin.
Raynaud’s Phenomena
 Is a problem of poor blood flow to fingers and toes.
 Blood flow decreases because blood vessels in these areas become
narrow for a short time, in response to cold or to emotional stress.
 Results in: finger sensitivity, toe sensitivity cold sensitivity, changes in
skin color, finger pain, toe pain, fingertip ulcers, toe ulcers
Raynaud’s Phenomena
Esophageal Dysmotility
 The digestive system includes the mouth, esophagus,
stomach, and bowels.
 Scleroderma can weaken the esophagus and the bowels.
 It can also build-up of scar tissue in the esophagus, which
narrows the tube.
Sclerodactyly
 When the fingers become tight, stretched, wax-like, and
hardened
Telangiectasias
 Telangiectasias are small enlarged blood vessels near the
surface of the skin, usually they measure only a few
millimetres.
 They can develop anywhere on the body but commonly on
the face around the nose, cheeks and chin
CREST
Treatment
 Those who suffer from scleroderma may have hope in a new
drug being tested at Wayne State University School of
Medicine.
 Phase II clinical studies of relaxin, a naturally occurring
hormone, show that the drug may reverse skin thickening,
which is a clinical measure of the progression of
scleroderma.
Laboratory Tests
 Presence of serum anti-Scl-70 antibodies
 Antinuclear antibody (ANA or FANA)
 Rheumatoid Factor (RF)
 Antibody to single stranded DNA (ssDNA)
 Soluble interleukin 2 receptor level (sIL 2 r).
The End