Table II.

Predominantly antibody deficiencies

Disease	Serum Ig	Associated features	Inheritance	Genetic defects/presumed pathogenesis
1. Severe reduction in all serum immunoglobulin isotypes with profoundly decreased or absent B cells
a) Btk deficiency	All isotypes decreased	Severe bacterial infections; normal numbers of pro-B cells	XL	Mutations in BTK
b) μ heavy chain deficiency	All isotypes decreased	Severe bacterial infections; normal numbers of pro-B cells	AR	Mutations in μ heavy chain
c) λ5 deficiency	All isotypes decreased	Severe bacterial infections; normal numbers of pro-B cells	AR	Mutations in λ5
d) Igα Deficiency	All isotypes decreased	Severe bacterial infections; normal numbers of pro-B cells	AR	Mutations in Igα
e) Igβ Deficiency	All isotypes decreased	Severe bacterial infections; normal numbers of pro-B cells	AR	Mutations in Igβ
f) BLNK deficiency	All isotypes decreased	Severe bacterial infections; normal numbers of pro-B cells	AR	Mutations in BLNK
g) Thymoma with immunodeficiency	All isotypes decreased	Infections; decreased numbers of pro-B cells	None	Unknown
h) Myelodysplasia	All isotypes decreased	Infections; decreased numbers of pro-B cells	Variable	May have monosomy 7, trisomy 8 or dyskeratosis congenita
2. Severe reduction in serum IgG and IgA with normal, low or very low numbers of B cells
Common variable immunodeficiency disorders*	Low IgG and IgA; variable IgM	All have recurrent bacterial infections. Clinical phenotypes vary: autoimmune, lymphoproliferative and/or granulomatous disease	Approximately 10% have a positive family history (AR or AD)	Alterations in TACI, BAFFR, Msh5 may act as contributing polymorphisms**
a) ICOS deficiency	Low IgG and IgA; normal IgM	-	AR	Mutations in ICOS
b) CD19 deficiency	Low IgG, IgA and IgM	-	AR	Mutations in CD19
c) XLP1***	All isotypes may be low	Some patients have antibody deficiency though most present with fulminant Epstein Barr Virus infection or Lymphoma	XL	Mutations in SH2D1A
3. Severe reduction in serum IgG and IgA with normal/elevated IgM and normal numbers of B cells
a) CD40L deficiency****	IgG and IgA decreased; IgM may be normal or increased; B cell numbers may be normal or increased	Opportunistic infections, neutropenia, autoimmune disease	XL	Mutations in CD40L (also called TNFSF5 or CD154)
b) CD40 deficiency****	Low IgG and IgA; normal or raised IgM	Opportunistic infections, neutropenia	AR	Mutations in CD40 (also called TNFRSF5)
c) AID deficiency	IgG and IgA decreased; IgM increased	Enlarged lymph nodes and germinal centres	AR	Mutations in AICDA gene
d) UNG deficiency	IgG and IgA decreased; IgM increased	Enlarged lymph nodes and germinal centres	AR	Mutations in UNG gene
4. Isotype or light chain deficiencies with normal numbers of B cells
a) Ig heavy chain deletions	One or more IgG and/or IgA subclasses as well as IgE may be absent	May be asymptomatic	AR	Chromosomal deletion at 14q32
b) k chain deficiency	All immunoglobulins have lambda light chain	Asymptomatic	AR	Mutations in kappa constant gene
c) Isolated IgG subclass deficiency	Reduction in one or more IgG subclass	Usually asymptomatic; may have recurrent viral/bacterial infections	Variable	Unknown
d) IgA deficiency associated with IgG subclass deficiency	Reduced IgA with decrease in one or more IgG subclass	Recurrent bacterial infections in majority	Variable	Unknown
e) Selective IgA deficiency	IgA decreased/absent	Usually asymptomatic; may have recurrent infections with poor antibody responses to carbohydrate antigens; may have allergies or autoimmune diseases.	Variable	Unknown
		A few cases progress to CVID, others coexist with CVID in the same family.
5. Specific antibody deficiency with normal Ig concentrations and normal numbers of B cells	Normal	Inability to make antibodies to specific antigens	Variable	Unknown
6. Transient hypogammaglobulinemia of infancy with normal numbers of B cells	IgG and IgA decreased	Recurrent moderate bacterial infections	Variable	Unknown

XL, X-linked inheritance; AR, autosomal recessive inheritance; AD, autosomal dominant inheritance; BTK, Burton tyrosine kinase; BLNK, B cell linker protein; AID, activation-induced cytidine deaminase; UNG, uracil-DNA glycosylase; ICOS, inducible costimulator; Ig(κ), immunoglobulin of κ light-chain type.

^*Common variable immunodeficiency disorders: there are several different clinical phenotypes, probably representing distinguishable diseases with differing immunopathogeneses; alterations in TACI , BAFFR and Msh5 sequences may represent contributing polymorphisms or disease modifying alterations.

^**A disease-causing effect has been identified for homozygous C140R and A181E TACI mutations.

^***XLP1 (X-linked lymphoproliferative syndrome) is also included in Table IV.

^****CD40L deficiency (X-linked hyper IgM syndrome) and CD40 deficiency are also included in Table I.