Table 1.

Primary B-cell Immunodeficiencies.

Diseasea	Genetic defect	Inheritanceb	Immunoglobulin level and antibody response	Associated features
Severe Reduction in All Serum Immunoglobulin Isotypes with Profoundly Decreased or Absent B Cells (Agammaglobulinemia)
BTK deficiency, X-linked agammaglobulinemia (XLA)	BTK	XL	All isotypes decreased in most, some have detectable immunoglobulins	Severe bacterial infections, normal numbers of pro-B cells
μ heavy chain deficiency	IGHM	AR	All isotypes decreased	Severe bacterial infections, normal numbers of pro-B cells
λ 5 deficiency	IGLL1	AR	All isotypes decreased	Severe bacterial infections, normal numbers of pro-B cells
Igα deficiency	CD79a	AR	All isotypes decreased	Severe bacterial infections, normal numbers of pro-B cells
Igβ deficiency	CD79b	AR	All isotypes decreased	Severe bacterial infections, normal numbers of pro-B cells
BLNK deficiency	BLNK	AR	All isotypes decreased	Severe bacterial infections, normal numbers of pro-B cells
PIK3R1 deficiency	PIK3R1	AR/AD	All isotypes decreased	Severe bacterial infections, decreased or absent pro-B cells
E47 transcription factor deficiency	TCF3	AD	All isotypes decreased	Recurrent bacterial infections
Severe Reduction in at Least 2 Serum Immunoglobulin Isotypes with Normal or Low Number of B Cells (CVID phenotype)
CVID of unknown gene defect	Unknown	AD or AR	Low IgG and IgA with low/normal IgM; poor antibody response	Variable clinical expression, most have recurrent sinopulmonary infections, enteropathy, autoimmune, granulomatous and/or lymphoproliferative complications
TACI deficiency	TNFRSF13B(TACI)	AD or AR	Low IgG and IgA and/or IgM	Variable clinical expression
BAFF receptor deficiency	TNFRSF13C (BAFF-R)	AR	Low IgG and IgM	Variable clinical expression
TWEAK deficiency	TWEAK (TNFSF12)	AD	Low IgM and A, lack of anti-pneumococcal antibody	Pneumonia, bacterial infections, warts, thrombocytopenia, neutropenia
CD19 deficiency	CD19	AR	Low IgG and IgA and/or IgM	Recurrent infections, may have glomerulonephritis
CD81 deficiency	CD81	AR	Low IgG, low or normal IgA and IgM	Recurrent infections, may have glomerulonephritis
CD20 deficiency	CD20	AR	Low IgG, normal or elevated IgM and IgA	Recurrent infections
CD21 deficiency	CD21	AR	Low IgG, impaired anti-pneumococcal response	Recurrent infections
LRBA deficiency	LRBA	AR	All isotypes decreased	Recurrent infections, enteropathy, autoimmune cytopenias, lymphoproliferative complications, endocrinopathy
CTLA4 deficiency	CTLA4	AD	All isotypes decreased	Recurrent sinopulmonary infections, enteropathy, autoimmune, and/or lymphoproli ferative c omplicati ons
PIK3CD mutation (GOF)	PIK3CD GOF	AD	All isotypes decreased	Severe bacterial infections; decreased or absent pro-B cells, EBV
NFκBI deficiency	NFKBI	AD	Normal or low IgG, IgA, IgM, low or normal B cells, low memory B cells	Recurrent sinopulmonary infections, COPD, EBV proliferation, autoimmune cytopenias, alopecia and autoimmune thyroiditis
NFκB2 deficiency	NFKB2	AD	Low serum IgG, A and M; low B cell numbers	Recurrent sinopulmonary infections, alopecia and endocrinopathies
Severe Reduction in Serum IgG and IgA with Normal/Elevated IgM and Normal Numbers of B cells (Hyper IgM syndrome)
CD40L deficiency	CD40LG	XL	IgG and IgA decreased, IgM increased	Bacterial and opportunistic infections
CD40 deficiency	CD40	AR	IgG and IgA decreased, IgM increased	Bacterial and opportunistic infections
AID deficiency	AICDA	AR	IgG and IgA decreased, IgM increased	Bacterial infections, enlarged lymph nodes and germinal centers
UNG deficiency	UNG	AR	IgG and IgA decreased, IgM increased	Enlarged lymph nodes and germinal centers
Isotype, Light Chain, or Functional Deficiencies with Generally Normal Numbers of B Cells
Ig heavy chain mutations and deletions	Mutation or chromosomal deletion at 14q32	AR	One or more IgG and/or IgA subclasses as well as IgE may be absent	May be asymptomatic
Kappa chain deficiency	IGKC	AR	All immunoglobulins have lambda light chain	Asymptomatic
Isolated IgG subclass deficiency	Unknown	?	Reduction in one or more IgG subclass	Usually asymptomatic, a minority may have poor antibody response to specific antigens and recurrent viral/bacterial infections
IgG subclass deficiency with IgA deficiency	Unknown	?	Reduced IgA with decrease in one or more IgG subclass	Recurrent bacterial infections
Selective IgA deficiency	Unknown	?	Very low to absent IgA with other iso types normal, normal subclasses and specific antibodies	Bacterial infections, autoimmunity mildly increased
Specific antibody deficiency with normal Ig levels and normal B cells	Unknown	?	Normal	Reduced ability to produce antibodies to specific antigens
Transient hypogammaglobulinemia of infancy	Unknown	?	IgG and IgA decreased	Normal ability to produce antibodies to vaccine antigens, usually not associated with significant infections
Selective IgM deficiency	Unknown	?	Absent serum IgM	Pneumococcal/bacterial infections

^aIg, Immunoglobulin.

^bAD, autosomal dominant; AR, autosomal recessive; XL, X-linked.