L7 - Autoinflammatory disease Flashcards
What are auto-inflammatory disease?
heterogenous group of inherited disorders
what is there an absence of in auto-inflammatory diseases?
high-titre antibodies
antigen specific auto-reactive T cells
What are some Autosomal DOMINANT hereditary periodic fevers?
TRAPS
MWS
What are some Autosomal RECESSIVE hereditary periodic fevers?
DIRA
DITRA
What causes the persistence of triggers in auto inflammatory disease?
Dysregulated cell activation/feedback
lack of counter-regulatory pathways
What auto-inflammatory diseases are caused by issues with IL-1beta?
CAPS
DIRA
What auto-inflammatory diseases are caused by issues with IL-36?
DITRA
What is receptor antagonist?
regulation
high receptor antagonist = competitive blocking of receptor
What is DIRA?
Deficiency of IL-1RA
sterile multifocal osteomyelitis
periotstitis
pustulosis
What is used to treat DIRA?
Anakinra
Injection IL-1RA
daily injections
What are an important source of IL-1?
Keratinocytes
What cells are important responders to IL-1?
T-cells
upregulate the adaptive immune response
What is gout?
urate crystals at joints
commonly big toe joint
What is psoriasis?
scaly red plaques
itchy
infiltration of lymphocytes and inflammatory cells into the epidermis
What IL is strongly up-regulated in psoriatic lesions?
IL36y
What does IL-36 induce?
IL-36 induces IL-8 in FIBROBLASTS and KERATINOCYTES
IL-8 attracts neutrophils
Is IL-36 active in its full length?
NO
No production of IL-8
What is the Koebner phenomenom?
psoriatic skin triggered by microtrauma or irritation
What is DITRA?
Deficiency in IL-36 antagonist
without RA, binding of accessory protein cannot occur
What is pustular psoriasis?
skin function impaired
electrolyte disturbance due to skin loss
What is the importance of processing in IL-1 cytokines?
require post translational cleavage for activation
What does IL-36y also require for activation?
N- terminal truncation
What is the molecule that cleaves IL-36?
Cathepsin S
