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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 (cross-react with streptococcal M-protein) 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.
What are Treatments for Psoriasis?
Effectiv
eness
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
ReferencesBerth-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) StressB) Genetic TendencyC) Environmental FactorsD) Hair loss
Study Question 2
• PSORS1 can be defined as…?A) An allele of a geneB) A class of MHCC) A LocusD) A haplotype
Study Question 3
• Which of the following Psoriasis treatments inhibits the transcription of IL-2?
A) CyclosporinB) AnthralinC) UVBD) Coal Tar
Study Question 4
• Which of the following is an appropriate definition of molecular mimicry
A) The non-random assortment of genesB) The body attacking self due to a similarity of a
self antigen and a foreign antigenC) Self reactivity due to the presence of a foreign
antigenD) 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?