Table 2. Additional inborn errors of... | Rockefeller University Press

Table 2.

Additional inborn errors of IL-6 family cytokines/receptors

Genetic defect	IL6ST	IL11RA	LIFR	OSM	OSMR^a	IL31RA^a	IL27RA
Inheritance	AR complete	AR	AR	AR	AD	AD	AR
Core syndrome	SWS	Craniosynostosis/dental abnormalities	SWS	Severe bone marrow failure	FPLCA	FPLCA	EBV susceptibility
Main clinical lesson	IL-6ST/gp130 is essential for skeletal/autonomic development	IL-11 controls craniofacial/dental development	LIFR is essential for skeletal/autonomic development	OSM supports hematopoiesis/bone marrow niche	OSMRβ skin axis implicated in pruritic amyloidosis	IL-31RA skin axis implicated in pruritic amyloidosis	IL-27 is nonredundant in anti-EBV immunity
Skin and pulmonary infections	Not reported	Not reported	Not reported	Not reported	Not reported	Not reported	Not prominent
Atopic dermatitis/eczema	+/−	Not reported	Not reported	Not reported	± association reported	Not reported	Not reported
Extrahematopoietic/developmental abnormalities	Skeletal dysplasia/neonatal lung dysfunction	Craniosynostosis, dental abnormalities	Skeletal dysplasia, pulmonary dysfunction, dysautonomia, urinary tract malformation	Not reported	Skin-limited amyloidosis; eosinophilic material in the skin	Skin-limited amyloidosis	Not reported
Hyper-IgE	Not reported	Not reported	Not reported	Not reported	Not reported	Not reported	Not reported
Eosinophilia	Not reported	Not reported	Not reported	Not reported	Not reported	Not reported	Not reported
Low memory B cells	Not reported	Not reported	Not reported	Not reported	Not reported	Not reported	+
Low Th17 cells	Not reported	Not reported	Not reported	Not reported	Not reported	Not reported	−
Impaired acute-phase/inflammatory responses	+	Not reported	Not reported	Not reported	Not reported	Not reported	Not reported
Impaired IL-6 signaling	+	−	ND	ND	ND	ND	−
Impaired IL-11 signaling	+	+	ND	ND	ND	ND	ND
Impaired LIF signaling	+	−	+	ND	ND	ND	ND
Impaired OSM signaling	+	−	ND	+ (ligand absent)	+/−	ND/not expected	ND
Impaired IL-31 signaling	ND	ND	ND	ND	+/−	ND/possibly affected in skin	ND
Impaired IL-27 signaling	+	−	ND	ND	ND	ND	+
Predominant compartment	Skeletal/mesenchymal	Craniofacial/mesenchymal	Skeletal/autonomic/mesenchymal	Hematopoietic niche	Skin/epithelial-stromal	Skin/epithelial-stromal	T cell anti-EBV immunity
Key references	(23)	(6, 20, 21)	(22)	(25)	(26, 27, 28)	(27)	(24)

Genetic defect	IL6ST	IL11RA	LIFR	OSM	OSMRa	IL31RAa	IL27RA
Inheritance	AR complete	AR	AR	AR	AD	AD	AR
Core syndrome	SWS	Craniosynostosis/dental abnormalities	SWS	Severe bone marrow failure	FPLCA	FPLCA	EBV susceptibility
Main clinical lesson	IL-6ST/gp130 is essential for skeletal/autonomic development	IL-11 controls craniofacial/dental development	LIFR is essential for skeletal/autonomic development	OSM supports hematopoiesis/bone marrow niche	OSMRβ skin axis implicated in pruritic amyloidosis	IL-31RA skin axis implicated in pruritic amyloidosis	IL-27 is nonredundant in anti-EBV immunity
Skin and pulmonary infections	Not reported	Not reported	Not reported	Not reported	Not reported	Not reported	Not prominent
Atopic dermatitis/eczema	+/−	Not reported	Not reported	Not reported	± association reported	Not reported	Not reported
Extrahematopoietic/developmental abnormalities	Skeletal dysplasia/neonatal lung dysfunction	Craniosynostosis, dental abnormalities	Skeletal dysplasia, pulmonary dysfunction, dysautonomia, urinary tract malformation	Not reported	Skin-limited amyloidosis; eosinophilic material in the skin	Skin-limited amyloidosis	Not reported
Hyper-IgE	Not reported	Not reported	Not reported	Not reported	Not reported	Not reported	Not reported
Eosinophilia	Not reported	Not reported	Not reported	Not reported	Not reported	Not reported	Not reported
Low memory B cells	Not reported	Not reported	Not reported	Not reported	Not reported	Not reported	+
Low Th17 cells	Not reported	Not reported	Not reported	Not reported	Not reported	Not reported	−
Impaired acute-phase/inflammatory responses	+	Not reported	Not reported	Not reported	Not reported	Not reported	Not reported
Impaired IL-6 signaling	+	−	ND	ND	ND	ND	−
Impaired IL-11 signaling	+	+	ND	ND	ND	ND	ND
Impaired LIF signaling	+	−	+	ND	ND	ND	ND
Impaired OSM signaling	+	−	ND	+ (ligand absent)	+/−	ND/not expected	ND
Impaired IL-31 signaling	ND	ND	ND	ND	+/−	ND/possibly affected in skin	ND
Impaired IL-27 signaling	+	−	ND	ND	ND	ND	+
Predominant compartment	Skeletal/mesenchymal	Craniofacial/mesenchymal	Skeletal/autonomic/mesenchymal	Hematopoietic niche	Skin/epithelial-stromal	Skin/epithelial-stromal	T cell anti-EBV immunity
Key references	(23)	(6, 20, 21)	(22)	(25)	(26, 27, 28)	(27)	(24)

AD, autosomal dominant; AR, autosomal recessive; SWS, Stüve–Wiedemann syndrome; FPLCA, familial primary localized cutaneous amyloidosis; EBV, Epstein-Barr virus; ND, not determined.

OSMR and IL31RA variants have been reported in the heterozygous state in patients with FPLCA, their functional consequences appear context- and variant-dependent and remain incompletely defined.

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