Auto inflammatory Disease

Question 1

What are auto inflammatory diseases? (3)

Answer 1

A heterogenous group of inherited disorders - spontaneous attacks of systemic inflammation without apparent autoimmune basis

Absence of high-titre autoantibodies and antigen specific autoreactive T cells

No evidence of auto-antigenic exposure

Question 2

Give two examples of auto inflammatory diseases? (2)

Answer 2

IL-1beta - autosomal-dominant cryopyrin-associated periodic syndromes – CAPS
- leads to DIRA

IL-36 - pustular Psoriasis / leads to DITRA

Question 3

Describe how an IL-1 receptor antagonist works (4)

Answer 3

IL-1 binds to it’s receptor which then triggers intra-cellular signalling pathways to the nucleus, resulting in pro-inflammatory agents being release dependant on cell type.

This is homeostatically regulated by endogenous IL-1ra (the body’s own anakinra), which can be masssively boosted by the administration of Kineret

Question 4

Signs of active IL-1 mediated disease (2)

Answer 4

Elevation of serum IL-1
IL-1ra as the body tries to supress this cytokine

Question 5

What is DIRA? (4)

Answer 5

Deficiency of IL-1RA
Autosomal recessive
Dominated by neutrophils - leads to inflammation in various parts of the body
Sterile multifocal osteomyelitis, periostitis, pustulosis

Question 6

What is the treatment for DIRA? (1)

Answer 6

Anakinra
IL-1 receptor antagonists

Question 7

What is an important source of IL-1? (1)

Answer 7

Keratinocytes

Question 8

What is gout? (1)

Answer 8

Pain in joints
Auto-inflammatory reaction - production of IL-B
Too much IL-1 because of crystals

Question 9

Therapy of Resistant Gout (1)

Answer 9

Anakinra (IL-1 blocker)

Question 10

What is IL-36 gamma involved with? (1)

Answer 10

Psoriasis

Question 11

What does IL-36 do? (3)

Answer 11

IL-36 making fibroblasts and keratinocytes to produce IL-8 - which is a chemokine which attracts neutrophils
Only the activated form of Il-36 activates IL-8

Question 12

What does deficiency in IL-36 antagonist lead to and describe the process? (1)

Answer 12

DITRA
Pustular psoriasis

IL-36 binds to receptor antagonist
Block signalling if a lot of IL-36
Recruitment of neutrophils
If no functional IL-36 receptor antagonist:
- inflammatory response uncontrolled

Question 13

IL-1 cytokines and the importance of processing

Answer 13

Most IL-1 cytokines require post translational cleavage for activation

IL-36γ also requires N-terminal truncation for activation

Specific protease of IL-36γ activation is unknown

LOOK AT NOTES FOR A DIAGRAM