Transcript lupus ppt for website

Systemic Lupus Erythematosis
The Immune System
Immunology Connection to
Tissue Engineering
•Develop methods to selectively block immune response
to engineered tissue
•Manipulate immune system tissues to prevent
autoimmune diseases
•Scaffold compatibility
Gender Differences in
Immune Response
• Females resist a variety of infections better
than males
• Females may reject transplanted organs
more rapidly
• Females have a higher frequency of
autoimmune diseases
What is Lupus?
• An autoimmune disease
• Your body can not adequately distinguish
between foreign materials (antigens) and its own
cells and tissues.
• The immune system directs the development of
antibodies that target bodily (antigens)
components.
• The auto-antibodies react with the bodies own
antigens, forming immune complexes which can
accumulate and cause increasing inflammationrelated damage.
What Causes Lupus?
• Cause unknown, but suspect
– Genetic factors
– Environmental factors
What Causes Lupus? (cont’d)
• Genetic causes
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Hereditary, but no single gene known to cause SLE
Some people more genetically prone to Lupus
5% of children with parents who have it develop Lupus
10% of Lupus patients also have a close relative with
the disease
– Chromosomes 1 and 6 associated with Lupus in certain
families
Observations to Support Genetic
Factors in Lupus
Clustering in families
Identical twins > fraternal
twins
Genetic factors in SLE
-> different disease frequencies in different ethnic groups
-> sibling recurrence-risk ratio ~15-20 (thus, if your sibling has SLE your risk is ~1% rather
than ~0.05%)
-> high clinical disease concordance among twins: 2-5% for dizygotic twins,
24-58% for monozygotic twins
-> complement deficient patients (rare) very frequently develop SLE (40-75%)
-> evidence for linkage to specific gene loci:
Environmental factors?
What Causes Lupus? (cont’d)
• Environmental causes
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Infections
Antibiotics
Ultra-violet light
Extreme stress
Certain drugs
Apoptosis and SLE: Causal
Connection?
• Delayed clearance of apoptotic cells
• Abnormal exposure of intracellular
components to immune response, supported
by autoantibody findings in Lupus patients
Complement and SLE?
• Altered complement system: an SLE
correlation?
• Reduced levels of C3 and C4 components
commonly found, those with C1, C2, and
C4 gene aberrations at apparent high risk
Symptoms of Lupus
• Flares are common
– Periods where symptoms are intense, then die down
• Most common symptoms
– Achy joints
• Occurs in 95% of Lupus patients
– Fever more than 100 degrees F
• 90%
– Arthritis
• 90%
– Prolonged or extreme Fatigue
• 81%
Symptoms of Lupus (cont’d)
– Skin rashes
• 74%
– Anemia
• 71%
• Other symptoms
– Kidney involvement, pain in chest, deep breathing,
butterfly shaped rash on cheek and nose, sun or light
sensitivity, hair loss, abnormal blood clotting,
Raynaud’s phenomenon, seizures, mouth and nose
ulcers.
SLE Characteristics
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Characterized by autoantibodies directed against nuclear and cytoplasmic
cellular components.
Result:
AutoAb-antigen immune complex formation, which circulate and deposit in
tissues, leading to chronic inflammation and continuous, extensive damage.
• Disease progresses in flares, followed by remissions
• Flares may include malaise, fever, joint pain, photosensitivity
• Lupus Flare (malar rash)
• Increased risk of clotting, stroke, heart disease, renal failure (advanced stages)
Lupus in Newborns
- up to 10% risk if mother has
certain antibodies
Clinical Features:
Reversible
skin
blood
liver
Irreversible
heart problems
Diagnosis of Lupus
• Difficult to diagnose Lupus
– Lupus symptoms mirror other diseases’ symptoms, and
Lupus symptoms often come and go
• No single lab test to diagnose Lupus
• American College of Rheumatology (ACR) issued
a list of 11 symptoms and tests to help diagnose
Lupus patients.
– A person with Lupus experiences at least four of these
symptoms or prove positive to at least 4 of these tests.
The symptoms do not have to occur at the same time
though.
SLE: Major diagnostic laboratory findings:
-> Positive lupus erythematosus cell preparation (a peculiar polymorphonuclear
leukocyte which has ingested nuclear material)
-> Hemolytic anemia, leukopenia, lymphopenia or thrombocytopenia
-> Heavy proteinuria or cellular casts in urine sediment
-> ***Anti-nuclear and/or anti-DNA antibodies***
Related systemic autoimmune diseases with overlapping findings:
-> Rheumatoid arthritis (mainly restricted to joints, distinguished by presence of RFs)
-> Sjogren’s symdrome (mainly restricted to salivary and lacrimal glands)
-> Schleroderma (mainly restricted to skin)
LE cell
1948
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ANA
Pathogenesis of SLE
Environmental
Triggers
Genetic Factors
Hormonal
Factors
Natural History of SLE
• Disease flares/activity (reversible)
• Organ damage (irreversible)
disease
treatment
SLE
Damage
SLE
Activity
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Time (years)
6
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Environmental Triggers
Sun exposure
(photosensitivity)
Drug-induced lupus
Viral triggers
Ultraviolet Irradiation Causes Programmed Cell Death
SLE Treatment
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NSAIDS
Antimalarials (HCQ Mepacrine)
Corticosteroids (oral/iv/im/intralesional)
Immunosuppressives
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Azathioprine
Cyclosporin A
Methotrexate
MMF
Cyclophosphamide
Biologicals- Rituximab
Others- Prasterone,Thalidomide,Acetretin
Interview of a Lupus Patient
• What kind of medications do you take?
– I take Plaquenil which is an anti-malarial drug that fights
fatigue. I also take Advil when I get stiff. I used to take
Prednisone, but I don’t have to anymore because my
disease isn’t as severe anymore as it used to be.
• Is there any research being done to find a cure or
better treatment for Lupus?
– There are many groups doing research on the immune
system which is a link to autoimmune diseases like
Lupus. Also, since Lupus seems to attack mostly women,
there are many groups trying to find a link between
hormones and Lupus.