C h a p t e r 1 6
Disorders of the Immune Response
359
Transient Hypogammaglobulinemia of Infancy.
During the first few months of life, infants are pro-
tected from infection by IgG antibodies that have been
transferred from the maternal circulation during fetal
life. Immunoglobulin A (IgA), IgM, IgD, and IgE do
not normally cross the placenta. The presence of ele-
vated levels of IgA or IgM in the infant cord blood
suggests premature antibody production in response to
an intrauterine infection. An infant’s level of maternal
IgG gradually declines over a period of approximately
6 months (see Chapter 15, Fig. 15-14). Concomitant
with the loss of maternal antibody, the infant’s imma-
ture humoral immune system begins to function, and
between the ages of 1 and 2 years, the child’s antibody
production reaches adult levels.
Any abnormality that interferes with the production
of immunoglobulin-producing plasma cells can produce
a state of immunodeficiency. For example, certain infants
may experience a delay in IgG production (IgM and IgA
levels are normal) beyond 6 months of age. The total
number and antigenic response of circulating B cells are
normal, but the chemical communication between B and
T cells that leads to clonal proliferation of antibody-pro-
ducing plasma cells seems to be reduced.
35
This condi-
tion is referred to as
transient hypogammaglobulinemia
of infancy.
The result of this condition usually is lim-
ited to repeated bouts of upper respiratory and middle
ear infections. This condition usually resolves by 2 to 4
years of age.
X-Linked Agammaglobulinemia.
X-linked (Bruton)
agammaglobulinemia is a recessive trait that almost
exclusively affects boys, as they have only one X
chromosome.
32–35,37,39
As the name implies, persons
with this disorder have essentially undetectable lev-
els of all serum immunoglobulins. Therefore, they
are susceptible to meningitis, recurrent otitis media,
and sinopulmonary infections with organisms such as
S. pneumoniae, H. influenzae
type b,
S. aureus,
and
Neisseria meningitidis.
33
The abnormal gene in X-linked agammaglobulinemia
that maps to the long arm of the X chromosome has a
role in all stages of B-cell development. Mutation in the
gene results in an absence of mature circulating B cells
and plasma cells. T lymphocytes, however, are normal
in number and function.
Most boys with the disorder remain asymptomatic
until 6 to 9 months of age because of the presence of
maternal antibodies. A clue to the presence of the disor-
der is the failure of an infection to respond completely
and promptly to antibiotic therapy. Diagnosis is based
on demonstration of low or absent serum immuno-
globulins. Therapy consists of prophylaxis with intrave-
nous immunoglobulin (IVIG) and prompt antimicrobial
therapy for suspected infections. The prognosis for this
condition depends on the prompt recognition and treat-
ment of infections. Chronic pulmonary disease is an
ever-present danger.
Common Variable Immunodeficiency.
A similar dis-
order of B-cell maturation is a condition called
common
variable immunodeficiency
(CVID). In this syndrome,
the terminal differentiation of mature B cells to plasma
cells is blocked.
35,37,38
More than 80% of persons with
this disorder have a normal number of B lymphocytes,
but they fail to differentiate into antibody-secreting
cells when the lymphocytes are presented with anti-
gen.
38
Some persons may also have increased apopto-
sis of helper T cells and decreased T-cell function and
signaling.
The symptomatology of CVID is similar to that of
X-linked agammaglobulinemia (i.e., recurrent otitis
Bone
marrow
Stem
cell
Pre-
B cell
IgG
1
IgG
2
IgG
3
IgG
4
Plasma
cell
Plasma
cell
Plasma
cell
Plasma
cell
Plasma
cell
B
C
C
A,C
C
D
C
B
lympho-
cyte
IgG
IgE
IgD
IgM
IgA
Differ-
entiation
Migration
to
lymphoid
tissue
Switching
Proliferation
FIGURE 16-6.
Stem cells
to mature immunoglobulin-
secreting plasma cells.
Arrows indicate the stage of
the maturation process that
is interrupted in
(A)
transient
hypogammaglobulinemia,
(B)
X-linked
agammaglobulinemia,
(C)
common variable
immunodeficiency, and
(D)
IgG subclass deficiency.
