Table 2. Shared and distinct clinical... | Rockefeller University Press

Table 2.

Shared and distinct clinical features of patients with inborn errors of the alternative NF-κB pathway

		AD NF-κB2 haploinsufficiency (p52^LOF/IκBδ^LOF)	AD p52-GOF (p52^GOF/IκBδ^LOF)	AD IκBδ-GOF (p52^LOF/IκBδ^GOF)	AR NIK deficiency	AR IKK-α deficiency	AR RelB deficiency	AD TRAF3 haploinsufficiency	AR BAFFR deficiency	AR LTBR deficiency	XL-CD40L or AR CD40 deficiency	AR RANK or RANKL deficiency
Gene		NFKB2	NFKB2	NFKB2	NIK	CHUK	RELB	TRAF3	BAFFR	LTBR	CD40/CD40L	RANK/RANKL
IEI/disease group		PAD	PAD	PAD	CID	CID	CID	Immune dysregulation	PAD	CID	CID	Osteopetrosis
Immunological phenotypes	B cells	↓ Ig, ↓ B cells, and ↑ mem B cells	↓ Ig and ↓ B cells	↓↓↓ Ig and ↓↓↓ B cells	↓↓↓ Ig and ↓↓↓ B cells	↓↓ Ig and ↓↓ B cells	↓↓ Ig and ↓↓ B cells	↑↑ Ig, ↑↑ B cells, and ↓↓ mem B cells	↓↓↓ Ig and ↓↓↓ B cells	↓↓↓ Ig and ↓↓↓ mem B cells	↑↑ IgM, ↓↓↓ IgG, and ↓↓↓ mem B cells	↓ Ig and ↓ mem B cells
Immunological phenotypes	T cells	Normal	Normal	↑ CD4⁺ naïve T, ↓ cTFh, and ↓ Treg	↑/↓ CD4⁺ naïve T and ↓ cTFh	↑ CD4⁺ naïve T, ↓ cTFh, and ↓ Treg	↓ CD4⁺ naïve T	↓ CD4⁺ naïve T, ↑ cTFh, and ↑ Treg	Normal	↓ cTFh and ↓ Treg	↓ cTFh	Normal
Susceptibility to infection	Respiratory tract bacterial infections	++	++	+++	+++	++	++	+++	++	+++	+++	±
	SARS-CoV-2, influenza, VZV, HSV-1	-	-	+++	++	+++	++	-	-	-	-	-
	Candidiasis (CMC)	-	-	-	+++	++	++	-	-	-	-	-
	Mycobacterial	-	-	-	++	-	-	-	-	-	-	-
	Cryptococcal	-	-	-	++	-	+	-	-	-	++	-
Syndromic features	Pituitary defects	-	-	++	-	-	-	-	-	-	-	-
	Alopecia areata/totalis	-	-	++	-	++	-	-	-	-	-	-
	Nail dystrophy	-	-	++	-	++	-	-	-	-	-	-
	Ectodermal dysplasia (sparse hair, eyebrows, or eyelashes)	-	-	+	-	++	-	-	-	-	-	-
SLO development	Lymph nodes	Normal	Lymphadenopathy	Normal	Hypoplasia	Hypoplasia	Hypoplasia	Lymphadenopathy	Normal	Hypoplasia	Normal/hypoplasia	Hypoplasia
SLO development	Spleen	Normal	Normal	Normal	Normal	Normal	Normal	Splenomegaly	Normal	Functional asplenia	Normal	Normal
Autoimmunity	Organ-mediated autoimmunity	++	+	++	-	++	++	++	-	-	-	-
Autoimmunity	Auto-Abs against type I IFNs	Negative	Negative	Positive	Positive	Positive	Positive	Negative	Negative	Negative	Negative	Negative

		AD NF-κB2 haploinsufficiency (p52^LOF/IκBδ^LOF)	AD p52-GOF (p52^GOF/IκBδ^LOF)	AD IκBδ-GOF (p52^LOF/IκBδ^GOF)	AR NIK deficiency	AR IKK-α deficiency	AR RelB deficiency	AD TRAF3 haploinsufficiency	AR BAFFR deficiency	AR LTBR deficiency	XL-CD40L or AR CD40 deficiency	AR RANK or RANKL deficiency
Gene		NFKB2	NFKB2	NFKB2	NIK	CHUK	RELB	TRAF3	BAFFR	LTBR	CD40/CD40L	RANK/RANKL
IEI/disease group		PAD	PAD	PAD	CID	CID	CID	Immune dysregulation	PAD	CID	CID	Osteopetrosis
Immunological phenotypes	B cells	↓ Ig, ↓ B cells, and ↑ mem B cells	↓ Ig and ↓ B cells	↓↓↓ Ig and ↓↓↓ B cells	↓↓↓ Ig and ↓↓↓ B cells	↓↓ Ig and ↓↓ B cells	↓↓ Ig and ↓↓ B cells	↑↑ Ig, ↑↑ B cells, and ↓↓ mem B cells	↓↓↓ Ig and ↓↓↓ B cells	↓↓↓ Ig and ↓↓↓ mem B cells	↑↑ IgM, ↓↓↓ IgG, and ↓↓↓ mem B cells	↓ Ig and ↓ mem B cells
Immunological phenotypes	T cells	Normal	Normal	↑ CD4⁺ naïve T, ↓ cTFh, and ↓ Treg	↑/↓ CD4⁺ naïve T and ↓ cTFh	↑ CD4⁺ naïve T, ↓ cTFh, and ↓ Treg	↓ CD4⁺ naïve T	↓ CD4⁺ naïve T, ↑ cTFh, and ↑ Treg	Normal	↓ cTFh and ↓ Treg	↓ cTFh	Normal
Susceptibility to infection	Respiratory tract bacterial infections	++	++	+++	+++	++	++	+++	++	+++	+++	±
	SARS-CoV-2, influenza, VZV, HSV-1	-	-	+++	++	+++	++	-	-	-	-	-
	Candidiasis (CMC)	-	-	-	+++	++	++	-	-	-	-	-
	Mycobacterial	-	-	-	++	-	-	-	-	-	-	-
	Cryptococcal	-	-	-	++	-	+	-	-	-	++	-
Syndromic features	Pituitary defects	-	-	++	-	-	-	-	-	-	-	-
	Alopecia areata/totalis	-	-	++	-	++	-	-	-	-	-	-
	Nail dystrophy	-	-	++	-	++	-	-	-	-	-	-
	Ectodermal dysplasia (sparse hair, eyebrows, or eyelashes)	-	-	+	-	++	-	-	-	-	-	-
SLO development	Lymph nodes	Normal	Lymphadenopathy	Normal	Hypoplasia	Hypoplasia	Hypoplasia	Lymphadenopathy	Normal	Hypoplasia	Normal/hypoplasia	Hypoplasia
SLO development	Spleen	Normal	Normal	Normal	Normal	Normal	Normal	Splenomegaly	Normal	Functional asplenia	Normal	Normal
Autoimmunity	Organ-mediated autoimmunity	++	+	++	-	++	++	++	-	-	-	-
Autoimmunity	Auto-Abs against type I IFNs	Negative	Negative	Positive	Positive	Positive	Positive	Negative	Negative	Negative	Negative	Negative

+, occasional; ++, commonly observed; +++, very frequent; CID, combined immunodeficiency; CMC, chronic mucocutaneous candidiasis; cTFh, circulating T follicular helper; mem, memory; PAD, predominantly antibody deficiency; SLOs, secondary lymphoid organs.

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