Table 1.
Monogenic autoinflammatory diseases
DiseaseKey regulatorTreatment targetReference
CAPS NLRP3
IL-1β
GSDMD
 
IL-1β (canakinumab)
IL-1R (anakinra)
IL-1 decoy receptor (rilonacept)
NLRP3 (MCC950)?
GSDMD? 
Goldbach-Mansky et al., 2006; Gattorno et al., 2007; Lachmann et al., 2009; Kitamura et al., 2014; Coll et al., 2015; Xiao et al., 2018  
FMF and PAAND Pyrin
IL-1β
TNF
IL-18?
GSDMD 
IL-1R (anakinra)
IL-1β (canakinumab)
IL-1 decoy receptor (rilonacept)
IL-18?
GSDMD? 
Hashkes et al., 2012; Sharma et al., 2017, 2019; Varan et al., 2019  
DIRA IL-1RA IL-1R (anakinra) Jesus and Goldbach-Mansky, 2014  
Blau syndrome/PGA NOD2
IL-1β 
IL-1R (anakinra)
IL-1β (canakinumab)
TNF 
Aróstegui et al., 2007; Simonini et al., 2013  
MKD/HIDS MVK
Pyrin
IL-1β 
IL-1R (anakinra)
IL-1β (canakinumab) 
Manthiram et al., 2017  
TRAPS TNFR
IL-1β
GSDMD?
MLKL? 
IL-1R (anakinra)
IL-1β (canakinumab) 
Jesus and Goldbach-Mansky, 2014  
Majeed syndrome LPIN2-NLRP3
IL-1β 
IL-1R (anakinra)
IL-1β (canakinumab) 
Jesus and Goldbach-Mansky, 2014  
PAPA syndrome PSTPIP1-Pyrin
IL-1β
IL-18? 
IL-1R (anakinra)
IL-1β (canakinumab)
TNF 
Kanameishi et al., 2017; Manthiram et al., 2017  
PFIT WDR1-Pyrin
IL-18
GSDMD? 
IL-18? Standing et al., 2017  
AIFEC NLRC4
IL-18
IL-1?
IFNγ? 
IL-18? Romberg et al., 2017  
NAIAD NLRP1
DPP9 
IL-1?
IL-18?
NLRP1?
GSDMD? 
Grandemange et al., 2017; Zhong et al., 2018  
NLRP12AD NLRP12
IL-1
GSDMD?
TNF? 
IL-1R (anakinra)? Jéru et al., 2011  
Chronic proliferative dermatitis Sharpin
TNF
RIPK1
RIPK3
MLKL
NLRP3
IL-1R
IL-1β 
TNF?
RIPK1 (Necrostatin-1)?
RIPK3 (GSK-872)?
MLKL (necrosulfonamide)
IL-1R (anakinra)?
NLRP3 (MCC950)?
GSDMD? 
HogenEsch et al., 1993; Gijbels et al., 1996; Gerlach et al., 2011; Kumari et al., 2014; Rickard et al., 2014; Gurung et al., 2016b  
DiseaseKey regulatorTreatment targetReference
CAPS NLRP3
IL-1β
GSDMD
 
IL-1β (canakinumab)
IL-1R (anakinra)
IL-1 decoy receptor (rilonacept)
NLRP3 (MCC950)?
GSDMD? 
Goldbach-Mansky et al., 2006; Gattorno et al., 2007; Lachmann et al., 2009; Kitamura et al., 2014; Coll et al., 2015; Xiao et al., 2018  
FMF and PAAND Pyrin
IL-1β
TNF
IL-18?
GSDMD 
IL-1R (anakinra)
IL-1β (canakinumab)
IL-1 decoy receptor (rilonacept)
IL-18?
GSDMD? 
Hashkes et al., 2012; Sharma et al., 2017, 2019; Varan et al., 2019  
DIRA IL-1RA IL-1R (anakinra) Jesus and Goldbach-Mansky, 2014  
Blau syndrome/PGA NOD2
IL-1β 
IL-1R (anakinra)
IL-1β (canakinumab)
TNF 
Aróstegui et al., 2007; Simonini et al., 2013  
MKD/HIDS MVK
Pyrin
IL-1β 
IL-1R (anakinra)
IL-1β (canakinumab) 
Manthiram et al., 2017  
TRAPS TNFR
IL-1β
GSDMD?
MLKL? 
IL-1R (anakinra)
IL-1β (canakinumab) 
Jesus and Goldbach-Mansky, 2014  
Majeed syndrome LPIN2-NLRP3
IL-1β 
IL-1R (anakinra)
IL-1β (canakinumab) 
Jesus and Goldbach-Mansky, 2014  
PAPA syndrome PSTPIP1-Pyrin
IL-1β
IL-18? 
IL-1R (anakinra)
IL-1β (canakinumab)
TNF 
Kanameishi et al., 2017; Manthiram et al., 2017  
PFIT WDR1-Pyrin
IL-18
GSDMD? 
IL-18? Standing et al., 2017  
AIFEC NLRC4
IL-18
IL-1?
IFNγ? 
IL-18? Romberg et al., 2017  
NAIAD NLRP1
DPP9 
IL-1?
IL-18?
NLRP1?
GSDMD? 
Grandemange et al., 2017; Zhong et al., 2018  
NLRP12AD NLRP12
IL-1
GSDMD?
TNF? 
IL-1R (anakinra)? Jéru et al., 2011  
Chronic proliferative dermatitis Sharpin
TNF
RIPK1
RIPK3
MLKL
NLRP3
IL-1R
IL-1β 
TNF?
RIPK1 (Necrostatin-1)?
RIPK3 (GSK-872)?
MLKL (necrosulfonamide)
IL-1R (anakinra)?
NLRP3 (MCC950)?
GSDMD? 
HogenEsch et al., 1993; Gijbels et al., 1996; Gerlach et al., 2011; Kumari et al., 2014; Rickard et al., 2014; Gurung et al., 2016b  

AIFEC, autoinflammation with infantile enterocolitis; DIRA, deficiency of IL-1R antagonist; HIDS, hyper IgD syndrome; MKD, mevalonate kinase deficiency; NLRP12AD, NLRP12-associated autoinflammatory disease; PAAND, Pyrin-associated autoinflammation with neutrophilic dermatoses; PAPA, pyogenic arthritis, pyoderma gangrenosum, and acne; PFIT, periodic fever, immunodeficiency, and thrombocytopenia; PGA, pediatric granulomatous arthritis; TRAPS, TNF receptor–associated periodic fever.

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