Chapter 21
Autoimmune Disease
M. Patricia Leuschen
Questions
1.
This molecule is hypothesized to be involved in degradation of the endothelial extra cellular matrix in
vasculitic neuropathy.
a. Integrin
b. Matrix metalloproteinase
c. TNFα
d. NF-kappa B
2.
This autoimmune disease affects men more frequently than women
a. Multiple sclerosis
b. Crohn’s Disease
c. Reiter’s Disease
d. Lupus erythematosus
3.
An autoimmune disease linked directly to an infectious etiology
a. Psoriasis
b. Rheumatoid arthritis
c. Alkylosing spondylitis
d. Systemic Lupus erythematosus
4.
Which of the following is NOT a structural/functional characteristic of the cerebrovascular endothelium?
a. extensive tight junctions
b. polarization apical-basal orientation of endothelial cells
c. association with astrocytic end plates
d. lower trans-endothelial electrical resistance
5.
Inflammation of the synovial joints in rheumatoid arthritis includes this change in the synovial fluid
a. Influx of macrophages and activated T cells
b. Loss of hyaluronic acid
c. Thinning of the synovial membrane
d. Presence of the bacterium Klebsiella
6.
HLA B27 allele has been identified in those at greater risk for all except this autoimmune disease
a. Alkylosing spondylitis
b. Psoriatic arthritis
c. Reiter’s disease
d. Crohn’s disease
7.
The primary type of nervous system involvement in Sjogren’s syndrome is
a. Spinal cord column involvement
b. Sensory ataxic neuropathy
c. Cervical cord involvement at the atlanto-axis junction
d. Autonomic neuropathy
8.
In systemic lupus erythematosus, this is a common neurologic involvement due to the chronic hypercoagulable state
a. Autonomic neuropathy
b. Dementia
c. Headache
d. Stroke
21. Autoimmune Disease
M. Patricia Leuschen
9.
2
Reiter’s disease commonly is diagnosed within this age range
a. <20
b. 20-40
c. 40-60
d. >60
10. Neurologic involvement in Crohn’s disease
a. Is relatively rare (<5%)
b. Usually occurs in 20%-30% of Crohn’s patients
c. Occurs in over 90% of Crohn’s cases
d. Is virtually always a peripheral neuropathy
11. Compare the gender distribution of those diagnosed with Multiple Sclerosis, Crohn’s disease and
Alkylosing Spondylitis.
12. Autologous haematopoetic stem cell transplantation AHSCT) has undergone phase I/II trials for several
autoimmune disorders. Aside from its invasive nature, discuss the pros and cons for its use.
13. Discuss the general mechanism of action for biologicals such as infliximab and etanercept.
14. Discuss the different hypothesized etiologies for neuropsychiatric SLE versus systemic SLE neuropathies.
15. Discuss the postulated role of molecular mimicry in Alkylosing Spondylitis.
16. What is the typical short and long-term course of Reiter’s disease?
17. Thalidomide is receiving new interest for use in some autoimmune conditions. What is the history and
concern for its use?
18. What is the anatomic basis for psoriasis in the skin?
19. Discuss how inflammation is both a positive and negative factor in autoimmune disorders.
20. Discuss the causes of vasculitis as it relate to vasculitic neuropathy.
21. Autoimmune Disease
M. Patricia Leuschen
3
Answers
1. b
2. c
3. c
4. d
5. a
6. d
7. b
8. d
9. b
10. b
11. Compare the gender distribution of those diagnosed with Multiple Sclerosis, Crohn’s disease and
Alkylosing Spondylitis.
Multiple Sclerosis occurs in women more than men at a ration of 2:1 or 3:1. Crohn’s disease occurs almost
equally in men and women. Alkylosing spondylitis occurs more frequently in young men.
12. Autologous haematopoetic stem cell transplantation AHSCT) has undergone phase I/II trials for several
autoimmune disorders. Aside from its invasive nature, discuss the pros and cons for its use.
There is evidence in Crohn’s disease that low levels of auto-antibodies return within 12 months after AHSCT
and that progression of pre-existing disability continues after AHSCT in MS. In both cases, AHSCT does not
“cure” the disease. However, HSCT is currently under trial only for those with very severe aggressive
autoimmune disease that is refractory to other treatment. For those patients it has significantly decreased
symptoms and increased quality of life.
13. Discuss the general mechanism of action for biologicals such as infliximab and etanercept.
Both are biologicals prepared using recombinant DNA technology and act as TNFα antagonists.
14. Discuss the different hypothesized etiologies for neuropsychiatric SLE versus systemic SLE neuropathies.
Neuropsychiatric SLE symptoms are hypothesized to be due to vascular lesions whereas systemic symptoms
may be related to autoantibody-mediated or cytokine mediated impairment of the neuronal function
15. Discuss the postulated role of molecular mimicry in Alkylosing Spondylitis.
B27, the HLA allele proposed to be involved in alkylosing spondylitis, shares an epitope with an enzyme from
Klebsiella pneumoniae, a common intestinal Gram negative bacterium. Molecular mimicry is thought to result
in cross-reactive antibody formation, joint inflammation and spinal damage
16. What is the typical short and long term course of Reiter’s disease?
Reiter’s syndrome usually develops within 2-4 weeks after a bacterial infection in susceptible individuals.
While Reiter’s syndrome typically has a limited course with symptoms lasting 3 to 12 months, it may recur. For
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M. Patricia Leuschen
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approximately 15-20% of those affected, Reiter’s develops into a chronic and often severe arthritis or
spondylitis.
17. Thalidomide is receiving new interest for use in some autoimmune conditions. What is the history and
concern for its use?
Biologic agents targeting specific sites in the immunoinflammatory cascade are being used to treat many
autoimmune disorders. Thalidomide whose effect is partially mediated by down regulation of TNF α has
efficacy in previously refractory autoimmune disorders such as Crohn’s patients. Historically Thalidomide was
used as a treatment for morning sickness during pregnancy and caused major upper extremity birth defects
before being removed from the market. It must be used with great care in any woman of child bearing potential.
18. What is the anatomic basis for psoriasis in the skin?
Normally, keratinocyte stem cells divide in the deepest layer of the skin’s epidermis, the stratum basale, to form
immature kertainocytes. These keratinocytes slowly mature and migrate toward the skin surface accumulating
more keratin as they go and eventually undergoing apoptotic cell death before being shed to make room for
underlying cells The cycle, normally takes about 30 days but in psoriasis, the keratinocytes move more quickly
from the statum basale to the stratum corneum of the epidermis where they are shed in as little as 7-10 days.
19. Discuss how inflammation is both a positive and negative factor in autoimmune disorders.
Inflammation is a hallmark of all the autoimmune disorders. While inflammation is associated negatively with
vasculitis and autoimmune disease, it is also necessary to protect normal cells from viral and bacterial infection.
Many of the therapies that act positively as immunosuppressants have an initial inflammatory response. While
IFNβ is an effective therapy in the inflammatory phases of MS, the initial response to each injection is an
increase in inflammatory cytokines, IL-2 and IFNγ.
20. Discuss the causes of vasculitis as it relate to vasculitic neuropathy.
The inflammation associated with vasculitic neuropathy occurs as a hypersensitivity reaction to antigens of
perceived non-self proteins. In vasculitic neuropathy, mononuclear cells in the perivascular infiltrate express T
cell restricted intracellular antigens, which induce apoptosis of other inflammatory mononuclear cells and may
affect recovery.