Immunology - Autoinflammatory + Autoimmune Flashcards
How are autoinflammatory and autoimmune diseases characterised?
Immunopathology in the absence of infection
Autoinflammatory = innate immune response
- Not characterised by auto-antibodies
- Weaker HLA associations
Autoimmune = Adaptive immune response
- Autoantibodies present
- HLA associations common
Mixed Disease = Mixed Innate/Adaptive
- Autoantibodies absent
- HLA associations possible
What are some rare monogenic autoinflammatory diseases?
- Familial mediterranean fever
- TRAPS
What are some polygenic autoinflammatory diseases?
- Crohn’s disease
- Ulcerative colitis
- Osteoarthritis
- Giant cell arteritis
- Takayasu’s arteritis
What are some mixed pattern diseases?
- Ankylosing spondylitis
- Psoriatic arthritis
- Behcet’s syndrome
What are some polygenic autoimmune diseases?
- Rheumatoid arthritis
- Myaesthenia Gravis
- Pernicious anaemia
- Graves disease
- SLE
- Primary biliary cirrhosis
- ANCA associated vasculitis
- Goodpasture disease
What are some rare monogenic autoimmune diseases?
- APS-1, APECED
- ALPS
- IPEX
What is the cause and characteristics of monogenic autoinflammatory diseases?
Cause:
- Mutations in gene encoding protein involved in pathway associated with innate immune cell function
Characteristics:
- Abnormal signalling via key cytokine pathways involving TNF +/- IL-1 is common
What is the pathogenesis of Familial Mediterranean Fever?
- Autosomal Recessive
- Mutation in MEFV gene
- Gene encodes pyrin-marenostrin
- Pyrin-marenostrin expressed mainly in neutrophils
- Failure to regulate cryopyrin driven activation of neutrophils
What is the clinical presentation of Familial Mediterranean Fever?
- Periodic fevers lasting 48-96hrs
- Abdo pain (peritonitis)
- Chest pain (Pleurisy + Pericarditis)
- Arthritis
- Rash
How is Familial Mediterranean Fever a long term risk of AA Amyloidosis?
- Liver produces serum amyloid A as acute phase protein
- Serum amyloid A deposits in kidneys, liver spleen
- Kidney deposition most clinically important
- Proteinuria = nephrotic syndrome
- Renal failure
What is the treatment for Familial Mediterranean Fever?
- Colchicine 500ug BD
- Anakinra (IL-1 receptor antagonist)
- Etanercept (TNF α inhibitor)
What is the MoA of Colchicine?
Binds ot tubulin in neutrophils + disrupts neutrophil functions (inc. migration + chemokine secretion)
What is a monogenic autoimmune disease?
Mutation of a protein involved in a pathway associated with adaptive immune cell function
What is APS1/APECED?
- Autoimmune Polyendocrine Syndrome Type 1
- Autoimmune PolyEndocrinopathy Candidiasis Ectodermal Dystrophy Syndrome
What is the abnormality in APS1/APECED?
Abnormality in central tolerance
What is the inheritance pattern of APS1/APECED?
Autosomal recessive
What is pathogenesis of APS1/APECED?
- Defect in autoimmune regulator AIRE
- AIRE = transcription factor involved in development of T cell tolerance in thymus
- Defect causes upregulation of expression of self-antigens by thymic cells + promotes T cell apoptosis
- Defect leads to failure of central tolerance causing auto-reactive T + B cells
What are the clinical features of APS1/APECED?
Multiple Auto-immune diseases:
- Hypoparathyroidism
- Addison’s
- Hypothyroidism
- Diabetes
- Vitiligo
- Enteropathy
Abs VS IL17 + IL22 leads to candidiasis
What is IPEX?
Immune dysregulation, polyendocrinopathy, enteropathy
What is the abnormality in IPEX?
Abnormality of regulatory T cells (failure of peripheral tolerance)
What is the inheritance of IPEX?
X-linked
What is the pathogenesis of IPEX?
- Mutations in Foxp3 causes failure to negatively regulate T cell responses
- Results in autoreactive B cells
- Foxp3 is required for development of Treg cells
What are some clinical features of IPEX?
Autoimmune diseases:
- Diabetes
- Hypothyroidism
- Enteropathy
- Diarrhoea
- Diabetes
- Dermatitis
What is ALPS?
Autoimmune lymphoproliferative syndrome
