Humoral Immunity Deficiencies

Disorder	Inheritance	Some Affected Genes	Clinical Findings
Common variable immunodeficiency	Variable	ARHGEF1, ATP6AP1, BAFFRCD19, CD27, CD81,CTLA4, CR2 CXCR4, DCLRE1C, GATA2, ICOS, IKZF1, IL21, IL21R, IRF2BP2, JAK3, KDM6A, KMT2D, LRBA, MS4A1, NFKB1, NFKB2, NSMCE3, PIK3CD, PIK3R1, PLCG2, PRKCD, RAC2, RAG1, RAG2, SH3KBP1, STAT3, STXBP2, TACI, TNFRSF13B, TNFRSF13C, TNFSF12, VAV1	Recurrent sinopulmonary infections, autoimmune disorders (eg, immune thrombocytopenia, autoimmune hemolytic anemia), malabsorption, giardiasis, granulomatous interstitial lung disease, nodular lymphoid hyperplasia of the GI tract, bronchiectasis, lymphocytic interstitial pneumonia, splenomegaly; in 10%, gastric carcinoma and lymphoma Usually diagnosed in patients aged 20–40 years
Hyper-IgM syndrome with AID or UNG deficiencies	Autosomal recessive	AID, UNG	Similar to X-linked hyper-IgM syndrome but with lymphoid hyperplasia No leukopenia
Hyper-IgM syndrome with CD40 deficiency	Autosomal recessive	CD40	Similar to X-linked hyper-IgM syndrome Lymphoid hypoplasia, neutropenia
Hyper-IgM syndrome with CD40 ligand deficiency	X-linked	CD40 ligand (CD40L)	Similar to X-linked agammaglobulinemia (eg, recurrent pyogenic bacterial sinopulmonary infections) but greater frequency of Pneumocystis jirovecii pneumonia, cryptosporidiosis, severe neutropenia, and lymphoid hypoplasia
Selective antibody deficiency with normal immunoglobulins	Unknown	—	Recurrent sinopulmonary infections Sometimes atopic manifestations (eg, atopic dermatitis, asthma, chronic rhinitis) Can occur in mild, moderate, severe, and memory phenotypes
Selective IgA deficiency	Unknown	In some cases, TACI	Most often asymptomatic Recurrent sinopulmonary infections, diarrhea, allergies (including anaphylactic reactions to blood products [rare]), autoimmune disorders (eg, celiac disease, inflammatory bowel disease, SLE, chronic active hepatitis)
Transient hypogammaglobulinemia of infancy	Unknown	—	Usually asymptomatic Sometimes recurrent sinopulmonary or GI infections, candidiasis, meningitis
X-linked agammaglobulinemia	X-linked	BTK	Recurrent sinopulmonary and skin infections during infancy, transient neutropenia, lymphoid hypoplasia Persistent CNS infections resulting from live-attenuated oral polio vaccine, echoviruses, or coxsackieviruses Increased risk of infectious arthritis, bronchiectasis, and certain cancers
AID = activation-dependent (induced) cytidine deaminase; ARHGEF1 = Rho guanine nucleotide exchange factor 1; ATP6AP1 = ATPase H+ transporting accessory protein 1;BAFFR = B-cell activating factor receptor; BTK = Bruton tyrosine kinase; C = complement; CAML = calcium-modulator and cyclophilin ligand; CD = clusters of differentiation; CD19 = CD19 molecule; CD27 = CD27 molecule; CD81 = CD81 molecule; CNS = central nervous system; CR2= complement receptor 2; CTLA4 = cytotoxic T-lymphocyte-associated protein 4; CXCR4 = C-X-C motif chemokine receptor 4; DCLRE1C = DNA cross-link repair 1C; GATA2= GATA binding protein 2; GI = gastrointestinal; ICOS = inducible T-cell co-stimulator; IKZF1 = IKAROS family zinc finger 1; IL21 = interleukin 21; IL21R = interleukin 21 receptor; IRF2BP2 = interferon regulatory factor 2 binding protein 2;JAK3= Janus kinase 3; KDM6A = lysine demethylase 6A; KMT2D = lysine methyltransferase 2D; LRBA = LPS responsive beige-like anchor protein; MS4A1 = membrane spanning 4-domains A1; NFKB1 = nuclear factor kappa B subunit 1;NKFKB2 = nuclear factor kappa B subunit 2; NSMCE3 = NSE3 homolog, SMC5-SMC6 complex component; PIK3CD = phosphatidyl 3-kinase catalytic subunit delta; PIK3R1 = phosphoinositide-3-kinase regulatory subunit 1; PLCG2 = phospholipase C gamma 2; PRKCD = protein kinase C delta; RAC2 = Rac family small GTPase 2; RAG1 = recombination activating 1; RAG2= recombination activating 2; SH3KBP1 = SH3 domain containing kinase binding protein 1; SLE = systemic lupus erythematosus; STAT3= signal transducer and activator of transcription 3; STXBP2 = syntaxin binding protein 2; TACI= transmembrane activator and CAML interactor; TNFRSF13B = TNF receptor superfamily member 13B; TNFRSF13C = TNF receptor superfamily member 13C; TNFSF12 = TNF superfamily member 12; UNG= uracil DNA glycosylase; VAV1 = vav guanine nucleotide exchange factor 1.

Disorder

Inheritance

Some Affected Genes

Clinical Findings

Variable

ARHGEF1, ATP6AP1, BAFFRCD19, CD27, CD81,CTLA4, CR2 CXCR4, DCLRE1C, GATA2, ICOS, IKZF1, IL21, IL21R, IRF2BP2, JAK3, KDM6A, KMT2D, LRBA, MS4A1, NFKB1, NFKB2, NSMCE3, PIK3CD, PIK3R1, PLCG2, PRKCD, RAC2, RAG1, RAG2, SH3KBP1, STAT3, STXBP2, TACI, TNFRSF13B, TNFRSF13C, TNFSF12, VAV1

Recurrent sinopulmonary infections, autoimmune disorders (eg, immune thrombocytopenia, autoimmune hemolytic anemia), malabsorption, giardiasis, granulomatous interstitial lung disease, nodular lymphoid hyperplasia of the GI tract, bronchiectasis, lymphocytic interstitial pneumonia, splenomegaly; in 10%, gastric carcinoma and lymphoma

Usually diagnosed in patients aged 20–40 years

Hyper-IgM syndrome with AID or UNG deficiencies

Autosomal recessive

AID, UNG

Similar to X-linked hyper-IgM syndrome but with lymphoid hyperplasia

No leukopenia

Hyper-IgM syndrome with CD40 deficiency

Autosomal recessive

CD40

Similar to X-linked hyper-IgM syndrome

Lymphoid hypoplasia, neutropenia

Hyper-IgM syndrome with CD40 ligand deficiency

X-linked

CD40 ligand (CD40L)

Similar to X-linked agammaglobulinemia (eg, recurrent pyogenic bacterial sinopulmonary infections) but greater frequency of Pneumocystis jirovecii pneumonia, cryptosporidiosis, severe neutropenia, and lymphoid hypoplasia

Selective antibody deficiency with normal immunoglobulins

Unknown

—

Recurrent sinopulmonary infections

Sometimes atopic manifestations (eg, atopic dermatitis, asthma, chronic rhinitis)

Can occur in mild, moderate, severe, and memory phenotypes

Selective IgA deficiency

Unknown

In some cases, TACI

Most often asymptomatic

Recurrent sinopulmonary infections, diarrhea, allergies (including anaphylactic reactions to blood products [rare]), autoimmune disorders (eg, celiac disease, inflammatory bowel disease, SLE, chronic active hepatitis)

Transient hypogammaglobulinemia of infancy

Unknown

—

Usually asymptomatic

Sometimes recurrent sinopulmonary or GI infections, candidiasis, meningitis

X-linked agammaglobulinemia

X-linked

BTK

Recurrent sinopulmonary and skin infections during infancy, transient neutropenia, lymphoid hypoplasia

Persistent CNS infections resulting from live-attenuated oral polio vaccine, echoviruses, or coxsackieviruses

Increased risk of infectious arthritis, bronchiectasis, and certain cancers

AID = activation-dependent (induced) cytidine deaminase; ARHGEF1 = Rho guanine nucleotide exchange factor 1; ATP6AP1 = ATPase H+ transporting accessory protein 1;BAFFR = B-cell activating factor receptor; BTK = Bruton tyrosine kinase; C = complement; CAML = calcium-modulator and cyclophilin ligand; CD = clusters of differentiation; CD19 = CD19 molecule; CD27 = CD27 molecule; CD81 = CD81 molecule; CNS = central nervous system; CR2= complement receptor 2; CTLA4 = cytotoxic T-lymphocyte-associated protein 4; CXCR4 = C-X-C motif chemokine receptor 4; DCLRE1C = DNA cross-link repair 1C; GATA2= GATA binding protein 2; GI = gastrointestinal; ICOS = inducible T-cell co-stimulator; IKZF1 = IKAROS family zinc finger 1; IL21 = interleukin 21; IL21R = interleukin 21 receptor; IRF2BP2 = interferon regulatory factor 2 binding protein 2;JAK3= Janus kinase 3; KDM6A = lysine demethylase 6A; KMT2D = lysine methyltransferase 2D; LRBA = LPS responsive beige-like anchor protein; MS4A1 = membrane spanning 4-domains A1; NFKB1 = nuclear factor kappa B subunit 1;NKFKB2 = nuclear factor kappa B subunit 2; NSMCE3 = NSE3 homolog, SMC5-SMC6 complex component; PIK3CD = phosphatidyl 3-kinase catalytic subunit delta; PIK3R1 = phosphoinositide-3-kinase regulatory subunit 1; PLCG2 = phospholipase C gamma 2; PRKCD = protein kinase C delta; RAC2 = Rac family small GTPase 2; RAG1 = recombination activating 1; RAG2= recombination activating 2; SH3KBP1 = SH3 domain containing kinase binding protein 1; SLE = systemic lupus erythematosus; STAT3= signal transducer and activator of transcription 3; STXBP2 = syntaxin binding protein 2; TACI= transmembrane activator and CAML interactor; TNFRSF13B = TNF receptor superfamily member 13B; TNFRSF13C = TNF receptor superfamily member 13C; TNFSF12 = TNF superfamily member 12; UNG= uracil DNA glycosylase; VAV1 = vav guanine nucleotide exchange factor 1.

In these topics

Overview of Immunodeficiency Disorders