AUTOIMMUNITY: AN UNMET
CLINICAL CHALLENGE
Overview
What is autoimmunity?
Septic Arthritis
Narcolepsy
Ankylosing Spondylitis
Treatment
What is autoimmunity?
Affects 5-8% of individuals in Western countries
Over 80 autoimmune conditions
Rheumatoid Arthritis, Diabetes Mellitus, Multiple Sclerosis
One of the least understood conditions in medicine
Among the leading causes of death in young and
middle aged women in the U.S.
Results from immune cells recognizing “self” as foreign.
Cause is unknown, but thought to occur one of two ways.
Molecular Mimicry
Error in T Cell Selection
T cells must undergo “positive” and “negative”
selection
Occurs before they are released into the body
Test cells against a piece of “self”
Strong reaction = deletion / cell death
Septic Arthritis
Caused by microbial infection
Septic = whole body infection ; presence of pathogens in
the bloodstream
Arthritis = joint inflammation
Easier to diagnose, usually only 1-2 joints involved
Strong immune reaction, many cells activated
Influx of cells to joint = inflammation
Leads to cartilage damage
Risk of septic shock because of high inflammation (blood
leaks out of capillaries, get decreased blood supply to
organs)
Risks in Septic Arthritis
Higher risk if individual has pre-existing joint disease
Taking drugs that suppress immune system
Also risk of molecular mimicry
May lead to more permanent arthritic complications
Borrelia burgdorferi is similar to our own cells
Narcolepsy
Chronic neurological disorder
1/2000 people
Results from inability to regulate sleep-wake cycles
Irresistible bouts of sleep throughout the day, length
varies
Only recently shown to be autoimmune
Reaction Against Protein in Narcolepsy
Lack of hypocretin =
hormone that promotes
wakefulness
Narcolepsy patients lack
cells that produce
hypocretin
Destroyed in autoimmune
reaction
Certain variation of
immune response gene is
present
Ankylosing Spondylitis
Affects 1.3% of adults 25 years and older = 2.4
million people
Angkylos = bent
Spondylos = spine
Belongs to subset of autoimmunity called the
spondyloarthropathies
Joint diseases of the spine associated with presence of
Damage in Ankylosing Spondylitis
Immune system cells attack spine
May be molecular mimicry component
Klebsiella pneumoniae
Causes tissue damage
Risk of spinal fracture in Ankylosing
Spondylitis
Current Treatment for Autoimmune
Disease
Manage symptoms
Methotrexate, Prednisone, Plaquenil, Arava
Therapeutic targets
Inhibit T cell activity
Induce T cell death
Eliminate certain subsets of T cells
Inhibit cytokine activity (anti-inflammatory) *
Modulate gene expression
Humira
Used for rheumatoid arthritis, psoriatic arthritis,
ankylosing spondylitis, Crohn’s disease
Slows joints damage, provides pain relief
Bind to cytokine from macrophage, relieves
inflammation and pain
Future Directions
Attempting to treat the source
Identify autoimmune T cells (Gocke et al., 2009)
Study structure; synthetic molecules could bind and inactivate
Track the development of the disease in hopes of
preventing it (Zangini et al., 2009)
Gene Therapy
Introduce anti-inflammatory genes into cells
Introduce TNF-α receptor genes into cells
Conclusions
Many factors affect immune system
Stress, environment, genetics, diet, sleep
Factors push cells one way or another.
Sometimes results in autoimmunity.
Need to be able to recognize autoimmunity in patients.
Research
The more we understand regulation and factors, the more
Thank you!
References
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