Table 3.

The mechanisms in monogenic autoinflammatory diseases

Innate mechanism	Component	Mechanism
Intracellular sensor function defects
CAPS (FCAS, MWS, NOMID/CINCA)	NLRP3 (cryopyrin)	Activation of NLRP3 inflammasome (gain‐of‐function) leading to IL‐1β production
FMF	Pyrin	Inflammasome activation, increased IL‐1β production
BS/PGA	NOD2	NF‐κB and RIP2K activation
CAMPS	Adaptor molecule C CARD14	Increased NF‐κB
Accumulation of intracellular triggers
TRAPS	Folding defect and accumulation of TNFR1	MAPK activation, Increased production of mROS, ER stress
CANDLE/PRAAS	Proteasome dysfunction	IFN response gene induction
HIDS/MKD	Mevalonate kinase	Lack of prenylation leads to cytoskeletal changes and inflammasome activation
Loss of a negative regulator of inflammation
DIRA	Loss of IL‐1 antagonism	Uncontrolled IL‐1 signalling
DITRA	Loss of IL‐36 antagonism	Uncontrolled IL‐36 signalling
EO‐IBD	Loss of IL‐10 or IL‐10 receptor antagonist	Decreased IL‐10 signalling
Effects on signalling molecules that upregulate innate immune cell function
AGS	Type I interferonopathy‐related proteins	Increased INF type I production

CAPS = Cryopyrin‐associated periodic syndrome; FCAS = Familial cold autoinflammatory syndrome; MWS = Muckle–Wells syndrome; CINCA = Chronic infantile neurological, cutaneous and articular syndromes; FMF = Familial Mediterranean fever; BS = Blau syndrome; PGA = Paediatric granulomatous arthritis; AGS = Aicardi–Goutières syndrome; CAMPS = CARD14‐mediated psoriasis; TRAPS = Tumour necrosis factor receptor‐associated periodic syndrome; CANDLE = Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature; PRAAS = Proteasome‐associated autoinflammatory syndrome; HIDS = Hyperimmunoglobulinaemia D with periodic fever syndrome; MKD = Mevalonate kinase deficiency; DIRA = Deficiency of IL‐I receptor antagonist; DITRA = Deficiency of IL‐36 receptor antagonist; EO‐IBD = Early‐onset inflammatory bowel disease.