Table Info

Table 1.

Targeted therapies and clinical use in PIRDs

Targeted treatment	PIRD
Cytotoxic agents
Anti-TNF-α monoclonal antibodies	CVID with ganulomas, IBD, or other autoimmunity
	TRAPS
	PAPA
	Blau syndrome [33]
	Mevalonate kinase deficiency [26–28]
	DIRA [26–28]
	Ataxia telangiectasia with granuloma [11–14]
	CTLA4 haploinsufficiency [102, 104]
	LRBA deficiency [21–24]
Cytokine inhibitors
IL-1 inhibitors	CVID with autoinflammation
	PAMI
	CAPS
	HA20
	DIRA
	NOMID [36]
	HLH
	APECED [29]
	FCAS [36]
	MWS [36]
	Majeed syndrome [48]
IL-4R inhibitors	IEIs with significant cutaneous atopy
	Wiskott Aldrich syndrome [61]
	ARPC1B deficiency
	DOCK8 deficiency [62–70]
	CARD11 deficiency [62–70]
	Netherton syndrome [62–70]
	RAG1/RAG2 immunodeficiency [62–70]
	STAT3 LOF [62–70]
	ZNF341 deficiency [62–70]
	STAT6 GOF [62–70]
	IPEX syndrome with atopic symptoms [62–70]
IL-5 inhibitors	STAT3 LOF with eosinophilic asthma [73, 74]
IL-5 inhibitors	IEI and coexisting atopic asthma
IL-6 inhibitors	Cytokine release syndrome in IEI
	SAVI [79, 80]
	SOCS1 [79, 80]
IL-12/23 inhibitors	CARD14 GOF disease
IL-18 inhibitors	Primary HLH in IEI [88]
	NLRC4 mutation [88]
	XIAP deficiency [88]
IFN-γ inhibitors	Primary HLH in IEI
Antibodies against specific immune cell molecules
B cell depleting agents	GLILD in CVID [91]
IgE depleting agents	STAT3 deficiency
Complement depleting agents	CHAPLE disease [99]
Small molecule inhibitors
CTLA4 analogs	CTLA4 insufficiency
	LRBA deficiency
	Rheumatoid arthritis [77]
	Juvenile idiopathic arthritis [77]
	Psoriatic arthritis [105, 106]
JAK inhibitors	STAT1 GOF
	STAT5b GOF
	STAT3 GOF
Kinase inhibitors
mTOR inhibitors	NLRC4 GOF [112]
	CTLA4 haploinsufficiency
	APDS
	ALPS [114, 115]
	ALPS like syndrome [116]
PI3K inhibitors	APDS [117–119]
Immunostimulants
IFN recombinant cytokines (IFN-γ)	CGD [89, 90]

PAPA: pyogenic arthritis, pyoderma gangrenosum and acne; DIRA: deficiency of IL-1R antagonist; PAMI: PSTPIP1-associated myeloid-related proteinemia inflammatory; CAPS: cryopyrin-associated periodic syndrome; HA20: haploinsufficiency of A20; NOMID: neonatal-onset multisystem inflammatory disorder; HLH: hemophagocytic lymphohistiocytosis; APECED: autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy; FCAS: familial cold autoinflammatory syndrome; MWS: Muckle-Wells syndrome; ARPC1B: actin-related protein 2/3 complex subunit 1B; DOCK8: dedicator of cytokinesis 8; CARD11: caspase recruitment domain-containing protein 11; RAG1: recombination activating gene 1; ZNF341: zinc finger protein 341; SAVI: STING-associated vasculopathy with onset in infancy; SOCS1: suppressor of cytokine signaling 1; NLRC4: NOD-like receptor family CARD domain-containing protein 4; XIAP: X-linked inhibitor of apoptosis; GLILD: granulomatous lymphocytic interstitial lung disease; CHAPLE: complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy; APDS: activated PI3K δ syndrome; ALPS: autoimmune lymphoproliferative syndrome; CGD: chronic granulomatous disease

Declarations

Author contributions

NM: Conceptualization, Methodology, Resources, Writing—original draft, Writing—review & editing. MG: Conceptualization, Methodology, Resources, Validation, Writing—review & editing, Supervision. VP, MW, JG, and TS: Investigation, Writing—original draft. GIK: Conceptualization, Writing—original draft, Writing—review & editing. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

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