Table 3. Genetic dissection of the... | Rockefeller University Press

Table 3.

Genetic dissection of the STAT3-HIES phenotypes based on inborn errors of the IL-6 family cytokine pathway

Deficiency	AR complete IL-6ST deficiency	AR partial IL-6ST deficiency	AD partial IL-6ST deficiency	AR IL-6Rα deficiency	AR IL-11Rα deficiency	AR LIFR deficiency	AR OSM deficiency	AR OSMRβ deficiency	OSMR missense heterozygous variants (FPLCA)	IL31RA missense heterozygous variants (FPLCA)
Affected signaling axis	Complete loss of multiple gp130-dependent cytokines	Partial defect of multiple gp130-dependent cytokines	Partial defect of multiple/specific gp130-dependent cytokines	IL-6 signaling	IL-11 signaling	LIFR-dependent cytokine signaling	OSM production/OSM signaling	OSM signaling; IL-31 R signaling likely altered	OSMR/IL-31 skin axis	IL31RA/IL-31 skin axis
Major clinical manifestations	Severe/frequently lethal SWS-like syndrome, neonatal respiratory dysfunction, skeletal abnormalities	HIES-like disease with recurrent infections, atopic dermatitis, hyper-IgE, eosinophilia, impaired acute-phase responses, craniosynostosis/developmental features	HIES-like disease with recurrent sinopulmonary infections, severe pulmonary complications, hyper-IgE/eosinophilia, retained deciduous teeth, skeletal/connective tissue features	Recurrent bacterial infections, defective acute inflammation, atopy, hyper-IgE, eosinophilia	Craniosynostosis, delayed tooth eruption, dental abnormalities, skeletal/connective tissue features	SWS, skeletal dysplasia, respiratory distress, dysautonomia, feeding difficulties, early death	Severe bone marrow failure, anemia, neutropenia, thrombocytopenia	Severe atopic dermatitis, hyper-IgE, eosinophilia, ± infections and HIES-like features	Pruritus, primary localized cutaneous amyloidosis, ± atopic dermatitis	Pruritus, primary localized cutaneous amyloidosis, ± atopic dermatitis

Deficiency	AR complete IL-6ST deficiency	AR partial IL-6ST deficiency	AD partial IL-6ST deficiency	AR IL-6Rα deficiency	AR IL-11Rα deficiency	AR LIFR deficiency	AR OSM deficiency	AR OSMRβ deficiency	OSMR missense heterozygous variants (FPLCA)	IL31RA missense heterozygous variants (FPLCA)
Affected signaling axis	Complete loss of multiple gp130-dependent cytokines	Partial defect of multiple gp130-dependent cytokines	Partial defect of multiple/specific gp130-dependent cytokines	IL-6 signaling	IL-11 signaling	LIFR-dependent cytokine signaling	OSM production/OSM signaling	OSM signaling; IL-31 R signaling likely altered	OSMR/IL-31 skin axis	IL31RA/IL-31 skin axis
Major clinical manifestations	Severe/frequently lethal SWS-like syndrome, neonatal respiratory dysfunction, skeletal abnormalities	HIES-like disease with recurrent infections, atopic dermatitis, hyper-IgE, eosinophilia, impaired acute-phase responses, craniosynostosis/developmental features	HIES-like disease with recurrent sinopulmonary infections, severe pulmonary complications, hyper-IgE/eosinophilia, retained deciduous teeth, skeletal/connective tissue features	Recurrent bacterial infections, defective acute inflammation, atopy, hyper-IgE, eosinophilia	Craniosynostosis, delayed tooth eruption, dental abnormalities, skeletal/connective tissue features	SWS, skeletal dysplasia, respiratory distress, dysautonomia, feeding difficulties, early death	Severe bone marrow failure, anemia, neutropenia, thrombocytopenia	Severe atopic dermatitis, hyper-IgE, eosinophilia, ± infections and HIES-like features	Pruritus, primary localized cutaneous amyloidosis, ± atopic dermatitis	Pruritus, primary localized cutaneous amyloidosis, ± atopic dermatitis

AD, autosomal dominant; AR, autosomal recessive; FPLCA, familial primary localized cutaneous amyloidosis; SWS, Stüve–Wiedemann syndrome; HIES, hyper-IgE syndrome.

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