Autoimmune Disorder: Psoriasis
Presented by:
Paige Barry
&
Chloe Janson
What is Psoriasis?
• Chronic skin disease that causes a rapid
growth of skin cells.
What are Symptoms of Psoriasis?
What is the Epidemiology of Psoriasis?
• Equally common in males and females
• Most common in 15-30 year olds;
– Can range from birth to 90 years old
• Effects 2-3% of total population (Psoriasis Vulgaris)
What are Triggers and Risk Factors?
• Medication Triggers
–
–
–
–
–
Lithium
Anti-Malarials
Quinidine
Indomethacin
Inderal
What is the Genetic Basis of Psoriasis?
What is the Genetic Basis of Psoriasis?
What is the Genetic Basis of Psoriasis?
• Strongest association with MHC class I
• Locus: Psoriasis susceptibility I (PSORS1)
• Located telomeric to the HLA-C region
• Strong association with HLA-Cw6 due to Linkage
Disequilibrium (non-random association of alleles at different
loci)
What is the Genetic Basis of Psoriasis?
• HLA-Cw*0602 is a high relative risk factor
• Study by Krueger and Bowcock said that HLA-Cw*0602 was
found in 10% of healthy controls and 50% of psoriasis patients
• No current studies have shown occurrences of psoriasis
independent of HLA-Cw6.
Cellular Interactions/Inflammation
• SLC9A3R1 is a scaffold protein in epithelial cells that sends
external signals to plasma membrane proteins
• Leads to alterations in signal transduction and cell growth and
may be involved in formation of the immune synapse.
• Dysregulation of this gene could delay the formation of the
synapse, increasing the time that antigen is presented to the T
cell receptor, hence leading to prolonged inflammation.
Cellular Interactions
• Psoriasis histopathology: neutrophils in the papillary dermis
and polymorphonuclear leucocytes (neutrophils) in the
stratum corneum
What is Molecular Mimicry?
• A foreign antigen shares sequence or structural
similarities with self-antigens
• Immune system attacks body due to shared antigens
How is Streptococci Recognized?
• A streptococci and is recognized by anti-M protein
monoclonal antibody (MAb) 10B6.
• Two C repeat peptides (C2A and C3) containing the
amino acid sequence KGLRRDLDASREAK react with
MAb 10B6
What is the Molecular Mimicry of
Psoriasis?
What is the Molecular Mimicry of
Psoriasis?
• Step 1: PG and M-protein
enter the bloodstream and
are taken up by
monocytes/macrophages
that migrate developing
psoriatic lesions.
What is the Molecular Mimicry of
Psoriasis?
• Step 2: Increased frequency
of CD4+ and CD8+ T cells in
blood.
What is the Molecular Mimicry of
Psoriasis?
• Step 3: Re-circulating CD4+
T cells migrate into the
lesional dermis.
What is the Molecular Mimicry of
Psoriasis?
• Step 4: CD8+ T cells migrate
through the dermis and into
the epidermis (required for
the characteristic
keratinocyte proliferation of
psoriasis).
What is the Molecular Mimicry of
Psoriasis?
• Step 5: Streptococcal
components (PG) are
presented in the dermis to
CD4+ T cells.
What is the Molecular Mimicry of
Psoriasis?
• Step 6: K peptides (crossreact with streptococcal Mprotein) are presented in
the epidermis to CD8+ T
cells.
What is the Molecular Mimicry of
Psoriasis?
• Step 7: APCs at the dermal–
epidermal junction can
present PG to CD4+ T cells
via HLA class II molecules.
What is the Molecular Mimicry of
Psoriasis?
• Step 8: APCs also present
keratin determinants to
CD8+ T cells via HLA class I.
Effectiveness
What are Treatments for Psoriasis?
Toxicity
How Do These Treatments Work?
• Cyclosporin: lowers activity of T cells
– Binds to cyclophilin of T cells
– Inhibits transcription of IL-2
– Leads to reduced function of effector T cells
How Do These Treatments Work?
• UVB: reduces dermal T cells and induces T-cell
apoptosis
– Downregulations the adhesion molecules that
recruit T cells from the blood into the skin
How Do These Treatments Work?
• Anthralin: restores the normal rate of
epidermal cell proliferation by reducing the
mitotic activity
– In vitro studies: prolongs the prophase of mitosis
for keratinocytes
– In vivo studies: inhibits DNA synthesis and
increases release of reactive oxygen species
References
Berth-Jones J. 2009. Psoriasis. Medicine 37(5):235-241.
Bowcock A, Krueger JG. 2005. Getting under the skin: the immunogenetics of psoriasis. Nature Reviews
Immunology 5(9): 699-711.
Gudjonsson, JE, Elder J. 2007. Psoriasis: epidemiology. Clinics in Dermatology 25(6): 535-546.
Krueger JG, Bowcock A. 2005. Psoriasis pathophysiology: current concepts of pathogenesis. Annuals of
Rheumatic Diseases 64(2): ii30-ii36.
Pardasani AG, Feldman SR, Clark AR. 2000. Treatment of Psoriasis: An Algorithm-Based Approach for Primary
Care Physicians. American Academy of Family Physicians 61(3): 725-733.
Valdimarsson H, Thorleifsdottir RH, Sigurdardottir SL, Gudjonsson JE, Johnston A. 2009. Psoriasis – as an
autoimmune disease caused by molecular mimicry. Trends in Immunology 30(10): 494-501.
Study Question 1
• Which of the following is not a trigger of
psoriasis?
A) Stress
B) Genetic Tendency
C) Environmental Factors
D) Hair loss
Study Question 2
• PSORS1 can be defined as…?
A) An allele of a gene
B) A class of MHC
C) A Locus
D) A haplotype
Study Question 3
• Which of the following Psoriasis treatments
inhibits the transcription of IL-2?
A) Cyclosporin
B) Anthralin
C) UVB
D) Coal Tar
Study Question 4
• Which of the following is an appropriate
definition of molecular mimicry
A) The non-random assortment of genes
B) The body attacking self due to a similarity of
a self antigen and a foreign antigen
C) Self reactivity due to the presence of a
foreign antigen
D) The decreased production of T cells in the
body due to immune system failure
Study Question 5
• A patient with horrible Psoriasis symptoms
complains that topical, photo, and systemic
treatments aren’t providing enough relief of
the symptoms. The doctor suggests that the
patient receive a tonsillectomy. Why might
this offer the patient greater symptomatic
relief?