Terry Kotrla, MS, MT(ASCP)BB

Topic 3 AutoimmunityPart 6 Diabetes

Part 7 Other Diseases

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; orPlasma 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 TestingTesting 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, 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.

TreatmentInjected insulin.Immunosuppressive drugs for newly

diagnosed patients.

Multiple Sclerosis

Multiple sclerosis (MS) is a chronic, potentially debilitating disease 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 SclerosisBecause 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 MSWithout 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 SclerosisMS 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.

DiagnosisThe 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 DiagnosisCerebrospinal 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

TreatmentThe 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

SymptomsFacial 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 TestingAutoantibodies 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 SyndromeAntibodies 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.

SymptomsSymptoms 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

DiagnosisComplete 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

TreatmentCorticosteroidsPlasmapheresisDialysis

Sjogren's SyndromeSjogren'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 SyndromeChronic 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 TestANA and RF positive

TreatmentNonsteroidal anti-inflammatory drugs

(NSAIDs), such as aspirin and ibuprofen Corticosteroids Saliva substitutes Artificial tears or eye drops Cyclosporine A (Restasis) eye drops

SclerodermaFrom 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 syndromeCalcinosisRaynaud’s PhenomenaEsophageal dysmotilitySclerodactylyTelangiectases

CalcinosisThe 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 PhenomenaIs 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

TelangiectasiasTelangiectasias 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

TreatmentThose 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 TestsPresence 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