autoimmune disorder: psoriasis presented by: paige barry & chloe janson

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?


• 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)


• 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?


• Step 1: PG and M-protein enter the bloodstream and are taken up by monocytes/macrophages that migrate developing psoriatic lesions.


• Step 2: Increased frequency of CD4+ and CD8+ T cells in blood.


• Step 3: Re-circulating CD4+ T cells migrate into the lesional dermis.


• Step 4: CD8+ T cells migrate through the dermis and into the epidermis (required for the characteristic keratinocyte proliferation of psoriasis).


• Step 5: Streptococcal components (PG) are presented in the dermis to CD4+ T cells.


• Step 6: K peptides (cross-react with streptococcal M-protein) are presented in the epidermis to CD8+ T cells.


• Step 7: APCs at the dermal–epidermal junction can present PG to CD4+ T cells via HLA class II molecules.


• 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


• UVB: reduces dermal T cells and induces T-cell apoptosis– Downregulations the adhesion molecules that

recruit T cells from the blood into the skin


• 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?

autoimmune disorder: psoriasis presented by: paige barry & chloe janson

Documents

guttate psoriasis

pustular psoriasis

psoriasis susceptibility

epidemiology of psoriasis

symptoms of psoriasis

genetic basis of psoriasis

molecular mimicry of

psoriasis autoimmune