5.2 Autoimmune Diseases

Define Autoimmunity.

Immune system mistakenly recognizes self tissue as foreign, and creates immune response

Self-tolerance is established by what 3 facts:

1. ability to identify and not react to self antigens

2. active regulation by T cells

3. a balance of T helper cell type 1 and 2

Which T helper cells are primary mediators of autoimmunity?

Th1 via cytokines

Inheritance of gene coding for a specific MHC molecule may make a person:

more susceptible to an autoimmune disease

MHC I complex will be on:

almost all nucleated cells

MHC II complex will be on:

APC

MHC III genes code for:

Complement

Define molecular mimicry:

Viral or bacterial antigens that resemble self antigens

What is an example of molecular mimicry?

Streptococcal infections causes Abs to develop that also recognize heart muscle Ags

What 2 types of cells are used for Antinuclear Antibodies (ANA) testing?

Mouse kidney or Human epithelial HEp-2 cells

What is an anti-nuclear antibody?

Ab formed to nuclear Ags that have been released into the blood (via apoptosis)

In Systemic Lupus Erythematosus (SLE) Where do the immune complexes commonly get trapped in the body?

• Kidneys

• Synovium

• Blood cells, vessels, skin, lungs, liver, nervous system, heart

What are the most common symptoms you would see with SLE?

When screening with the ANA test what 2 patterns would you find for SLE?

*For SLE, what are they specifically staining in the cell during ANA test?

Antinuclear antibodies

• ds-DNA (most specific)

What happens to complement levels in SLE? Why?

Decreased Complement due to activation of complement by immune complexes (i.e. consumption)

What is the substrate of the confirmation test for SLE, that has ds-DNA in the kinetoplast?

Crithidia luciliae (hemoflagellate)

What type of antibody is seen in Drug induced SLE? What pattern?

anti-histone

What is a common but separate antibody seen with SLE?

Anti-phosholipid

What are the most common antibodies tested for Antiphospholipid syndrome?

Anti-cardiolipin, lupus anticoagulant, β2-glycoprotein-1

What does Antiphospholipid syndrome cause in the patient?

• multiple miscarriages

• clotting issues

• migraines

• thrombotic events

What are some common abnormal labs seen in Antiphospholipid Syndrome?

• prolonged PTT

• low platelets

In Rheumatoid Arthritis (RA) Ig__ or Ig__ antibodies are formed against the ____ portion of ______.

IgM or IgG; Fc portion of IgG

What type of hypersensitivity is RA?

Type III

What are the 3 most common characteristic symptoms of RA:

1. Bilateral damage

2. Decreased joint space

3. Bony erosions

What is the screening test for RA called?It detects what type of Ab?

Screening Test: Rheumatoid Factor (RF)

• detects serum IgM

What is the confirmatory test for RA called?

Confirmatory Test: Anti-cyclic citrullinated peptide assay (anti-CCP)

_________ titers of complement will happen with RA

Low

What are the 4 main organ specific AI diseases?

In Hashimoto’s Thyroiditis, autoAbs are produced against _______________ and ____________ cell components

Thyroglobulin and Thyroid

Hashimoto’s Thyroiditis: ____ TSH (________thyroidism)

High TSH; hypothyroidism

What type of hypersensitivity is Hashimoto’s

Type II

Main symptoms for these Hashimoto are:

• Weight gain, lethargy, intolerance to cold

• Goiter, enlarged thyroid, hypothyroidism, thyroid autoantibodies

Hashimoto’s:
__________ ____________ Antibody is seen in 90-95% of pts

Thyroid Peroxidase Ab (TPO Ab)

Hashimoto’s:

__________ antibody is seen in 80% of pts but may also be seen in_______cancer pts

Thyroglobulin Ab (TgAb); thyroid

Graves’s Disease:

____ TSH (_________thyroidism)

Low TSH; Hyperthyroidism

What type of hypersensitivity is Grave’s Disease?

Type II

Main symptoms for Graves’ Disease:

• Thyrotoxicosis

• diffusely enlarged soft goiter

• Exophthalmos (35%)

• Weight loss, tremors

• Anxiety, difficulty sleeping, ↑ heart rate

• Heat intolerance

Graves’:

__________ ____________ Antibody is seen in ~75% of pts

Thyroid Peroxidase Ab (TPOAb)

Graves’:

__________ ____________ ________________ are a better Ab to help diagnose

Thyroid-Stimulating Immunoglobulins (TSI)

Thyroid-Stimulating Immunoglobulins (TSI) will lead to continual production of _____ & _____

T3 & T4

Type 1 Diabetes Mellitus results from destruction of _______ ______ in the ____________.

beta cells; pancreatic islets

What are the 4 most common AutoAbs of βcell autoimmunity?

1. Abs to GAD (glutamic acid decarboxylase)

2. ICA = islet cell Abs

3. Insulin autoAbs, Insulin-associated Ag (IAA)

4. Abs to transmembrane protein, tyrosine phosphatase (IA-2A)

Glucose/A1C values that indicate DM

• Fasting Plasma Glucose ≥ 126 mg/dL

• Random Plasma Glucose ≥ 200 mg/dL

• Hemoglobin A1c ≥ 6.5%

• Failing Oral Glucose Tolerance Test

T1DM:

Why would AutoAb testing be done for patients?

To screen for Type 1 DM before beta-cell destruction

• only for family members of T1DM

Addison’s Disease results from destruction or dysfunction of the _________ __________.

adrenal glands

For Addision’s Disease, List which classes of adrenal steroids will be deficient:

Main symptoms for Addisons pts are:

• Fatigue, weakness, loss of appetite/weight, salt cravings, ab pain, nausea/vomiting, muscle pain

• Low BP, dehydration, low blood sugar

  • May progress to shock and or death

Addison’s Disease:

____ glucose, cortisol, aldosterone, Na, Cl

decreased

Addison’s Disease:

____ K and renin levels

Increased

Addison’s Disease pts can also have Abs against ______________________

21-hydroxylase

Myasthenia Gravis results from Abs against ______________ ______________ at _______ _____

Acetylcholine Receptors at Neuromuscular Junctions

Myasthenia Gravis clinical signs

• Drooping eyelids

• Inability to retract the corners of the mouth

• Inability to maintain support of the trunk, the neck, or the head

Multiple Sclerosis is an inflammatory AI disorder of the __________.

CNS

In Multiple Sclerosis, what important component is destroyed by AutoAbs?

myelin sheath

Another important characteristic of MS is: _____________ formation in the white matter of the _____

plaque; brain

MS Main symptoms

In MS, what key characteristic is seen with CSF electrophoresis?

Oligoclonal Bands

How is MS confirmed? What are they looking for?

Confirmed with MRI

• looking for white matter plaques in brain and spinal cord

Celiac Disease results from an intolerance to dietary ___________ causing poor______________ of nutrients

gluten; absorption

What are some key clinical signs of Celiac pts

• Adults

  • Anemia (Fe def), diarrhea, bloating, fatigue, weight loss

• Kids

  • Irritability, abdominal distention, diarrhea, failure to thrive, weight loss

What are the 3 most common AutoAbs found in Celliac’s:

1. Anti-Tissue Transglutaminase (TTG)

2. Anti-Gliadin

3. Anti-Endomysial (component of lining within intestine)

Goodpasture’s Syndrome is due to an AutoAb towards the ______________, ______________, and _______

• glomerular

• renal tubular

• alveolar basement membrane

In Goodpasture’s Syndrome, damage to the glomerulus rapidly progresses to _________ __________

renal failure

Goodpasture’s Syndrome:

Glomerular damage is done by ______________ antibody making it a type ___hypersensitivity

cytotoxic; Type II

Goodpasture’s clinical signs

Goodpasture’s Treatment:

________________ can help remove circulating antibodies

Plasmapheresis

Scleroderma is a disorder that results in normal tissue/skin being replaced with:

Thick Tissue ( extra collagen produced)

Scleroderma will eventually lead to ____ when organs are changed (heart, lung, kidneys)

death

What does CREST (Scleroderma symptoms) stand for ?

Scleroderma ANA will show ____________ or _____________ pattern

speckled or nucleolar (95%)

___________ antibody is specific for Scleroderma but only seen in 15-20%

Scl-70

In Scleroderma___________ antibody is a marker for ________ .

Centromere; CREST

Sjögren’s Syndrome, an AI that affects the __________ glands, causing mostly dry ________and____

exocrine; dry eyes and mouth

Sjögren’s Syndrome has a____________ pattern

speckled

What are the 2 Sjögren’s Syndrome AutoAbs

1. Anti- SS-A/ Ro

2. Anti- SS B/ La

AI Diseases Summary Chart