Genetics of Inflammatory Disease Flashcards
Definition of autoinflammatory
Abnormal activation of the innate immune system
Definition of autoimmune
Abnormal response leading the loss of immune tolerance against self tissues by presence of autoreactive T and B cells
Describe the spectrum of autoinflammatory and autoimmune diseases
AF
- rare monogenic AF disease
- polygenic AF disease (IBS)
- mixed pattern diseases (psoriasis)
- polygenic AI disease (SLE)
- rare monogenic AI disease
Describe psoriasis
- what is it characterised by
- describe clinical presentation and triggers
- what are the risk factors
Common, life long genetic AI skin disease
Characterised by areas of thick, red, scaly skin
- v disorganised stratum corneum, infiltrated by neutrophils
- stratum spinosum and basale filled with smaller immature cells
Huge variation in
- clinical presentation
- triggers=> leads to impaired differentiation and hyperproliferation of keratinocytes
Describe the properties of ulcerative colitis
Inflammation/ulcers only in the colon mucosa
Superficial inflammation
Continuous inflammation
Describe the properties of Crohn’s disease
Inflammation of all GI tract layers
Full thickness inflammation
Patchy inflammation
What are the risks associated with IBD
What are the causes of IBD
Extra intestinal manifestations
Cancer risk
Caused by
- susceptibility genes
- persistent infection
- defective mucosal integrity
- dysregulated immune response
- dysbiosis
Describe the properties of Systemic Lupus Erythematosus
AI disease with unknown aetiology
Multisystemic disease involving autoantibody production
- nuclear antigens
- cellular antigens
- cell surface antigens
- serum components
What are the common properties shared by many AI, AF diseases
All have a variety of
- prevalences
- sex bias
- ethnicities
- age of onset
- risk factors
Describe the relationship between susceptibility loci and complex diseases
Many loci can contribute to a disease
-many overlap and are associated with many complex diseases
Found with GWAS
What were the therapies used for autoimmune disease in the past
Limited clinical efficacy
- non selective immunosuppresion
- cytotoxic drugs
What are the properties of current biological therapies for AI diseases now
Have increased efficacy, faster onset
Expensive
Inadequate response
Some severe AE
What are the potential treatments for AI disease
Evidence from GWAS
- indicate specific drug targets
- likely responders
Companies could market 1 drug for many diseases due to overlap of susceptibility loci between diseases
What are the 3 potential applications of GWAS data in clinical scenarios
Drug development for different groups to reduce AE
Diagnostic test development
Devise prevention/non drug strategies
