Selective B Cell Immunodeficiency

Question 1

What is agammaglobulinemia/X linked Btk deficiency?

Answer 1

T+B-NK+
Absent Ig levels
X linked mutation in Btk causing early B cell development arrest at the pre-B cell stage
Leads to absence of circulating B cells
Also results in defective rearrangement of heavy chain genes

Question 2

Which infections are most common in those with agammaglobulinemia and X linked Btk deficiency?

Answer 2

Recurrent bacterial infections

Question 3

What vaccines should be avoided for those with agammaglobulinemia and X linked Btk deficiency?

Answer 3

No live vaccines

Question 4

Which B cell immunodeficiencies can be treated with HSCT?

Answer 4

Agammaglobulinemia, X linked Btk deficiency and common variable immune deficiency (CVID)

Question 5

Which B cell immunodeficiencies can be treated symptomatically?

Answer 5

IgA and IgG deficiencies, hyper IgM and transient hypogammaglobulinemia of infancy

Question 6

Which B cell immunodeficiencies have no vaccine restrictions?

Answer 6

IgA and IgG subclass deficiencies

Question 7

Polio vaccine is not recommended for which B cell immunodeficiencies?

Answer 7

Hyper IgM, transient hypogammaglobulinemia of infancy and CVID

Question 8

What is IgG deficiency?

Answer 8

T+B+NK+
IgG absent, normal everything else
Caused by defects in several genes
Mostly asymptomatic but can present with recurrent bacterial infections
Low IgG2 = poor response to polysaccharide Ags in children

Question 9

What is IgA deficiency?

Answer 9

T+B+NK+
Absent IgA, normal everything else
Caused by mutation of terminal differentiation
Mostly asymptomatic but can present with recurrent bacterial infections
Related to autoimmune disease and allergies

Question 10

Why are 50% of IgA deficiency pts asymptomatic?

Answer 10

Due to IgM translocation across mucosal epithelium

Question 11

What is hyper IgM syndrome?

Answer 11

T+B+NK+
High IgM, low everything else
Impaired class switching and somatic hypermutation
Peripheral B cells are normal, but no CD27+ memory B cells
Increased susceptibility to bacterial infections
Ex. X linked CD40 (males) is 2/3 of all cases and autosomal CD40 deficiency (males and females) is 1/3 of all cases

Question 12

What is transient hypogammaglobulinemia of infancy?

Answer 12

T+B-/+NK+
Normal IgM, low IgG and IgA
Intrinsic Ig production delayed for up to 36 mo causing increased susceptibility to sinopulmonary infections
Ig concentrations normalize between 2-4 y/o

Question 13

What is common variable immune deficiency (CVID)?

Answer 13

T+B-/+NK+
Low IgG and IgA, sometimes low IgM
Characterized by defect in Ab production associated w/ hypogammaglobulinemia
Dx = hx of pyogenic sinopulmonary infections (at 20-30 y/o)
Leads to recurrent infections, autoimmune disease and lymphomas

Question 14

Which two deficiencies lead to opportunistic encapsulated infections?

Answer 14

Hyper IgM and transient hypogammaglobulinemia