AutoInflammatory Disease Flashcards
(39 cards)
What is an auto inflammatory disease?
Disease driven by components of the innate immune system
What is an autoimmune disease?
Disease driven by components of the adaptive immune system (usually due to breaking of tolerance of B/T cells, leading to development of immune-reactivity towards self antigens)
Which diseases have a function mutation in NLRP3?
muckle wells syndrome
Familial cold auto-inflammatory syndrome
Chronic infantile neurological cutaneous articular syndrome
What does the gain of function mutation in NLRP3 lead to?
CRYOPYRIN protein formation
CRYOPYRIN is an up regulator in the inflammatory pathway
What mutation occurs in Familial Mediterranean fever?
MEFV
What does MEFV mutation encode?
Pyrin-Marenostrin (expressed by neutrophils)
This is a negative regulator of the inflammatory pathway
What is the genetic propagation of Familial Mediterranean fever?
Autosomal Recessive
What is the clinical presentation of Familial Mediterranean fever?
Periodic fevers (48-96 h) due to:
- abdo pain, due to peritonitis
- chest pain, due to pleurisy/pericarditis
- arthritis
- rash
What disease is Familial Mediterranean fever associated with long term?
AA amyloidosis (as the livery produces serum amyloid A as an acute phase protein, which would then deposit in kidneys, liver, spleen)
What is treatment for Familial Mediterranean fever?
COLCHICINE 500mg BD
Disrupts neutrophil function)
What other medications can we give for Familial Mediterranean fever?
Anakinra
Etanercept
What are the three types of pathogenesis in MONOGENIC autoimmune DISEASE?
- abnormality of tolerance: APS1, APECED
- abnormality of regulatory T cells - IPEX
- abnormality of lymphocyte apoptosis - ALPS
What is the aetiology of APECED/APS1
Defect in AIRE (transcription factor for development of T cell tolerance in thymus. It upregulates expression of self-antigens by thymic cells which T cells are selected against, and promotes apoptosis of auto-reactive T cells)
What does the defect in AIRE lead to?
Failure of central tolerance, release of auto-reactive T cells
What diseases occur in APECED?
Hypoparathyroidism
Addisons dsisease
Candisiases
What mutation causes IPEX?
Foxp3
What is Foxp3 required for?
For development of Treg cells (which negatively regulate T cell response)
What occurs in IPEX
Lack of Treg cells > patients fail to -vely regulate T cell response > AUTOANTIBODY formation > AI disease
What are common AI diseases in IPEX?
Enteropathy
DM
Hypothyroidism
Dermatitis
What mutation causes ALPS?
FAS pathway mutation (heterogeneous)
What occurs in ALPS?
Defect in apoptosis of lymphocytes (as Fas is dysfunctional)
What is the clinical phenotype in ALPS?
High lymphocyte count
Large spleen and large lymph nodes
AI disease
Lymphoma
What is the most known gene mutation for Chron’s?
NOD2
What kind of genetic disease is Chron’s?
Polygenic
