Case 6
Manzhu Kang, Phil Soto, Ivana Olguin
California State University, Los Angeles
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Clinical manifestations:
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Lab Results:
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Recurrent Pneumonia, otitis media, erysipelas since 2 years old.
Atelectasis, chronic cough, no visible tonsil, moist crackles at both
lung bases at age of 9.
Very low level of IgG and IgM, no IgA, normal white blood cell
count
Family History:
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2 brothers of his mother died from pneumonia at age of 2, but 2
healthy sisters who have a healthy son and daughter
One younger sibling with similar symptoms
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Recurrent infections since age of 2
Very low level of serum
immunoglobulins
Absent tonsils
Family history
X-linked
Agammaglobulinemia
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Immunoelectrophoresis
reveals the absence immunoglobulin in serum
B cells level in the peripheral blood by flow
cytometry with no or very little B cells
Genetic testing to detect mutation in Xchromosome
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Immunoglobulin replacement by weekly
subcutaneous injection or intravenous infusion
every 2-4 weeks, for life.
Chronic prophylactic antibiotics are used in
some centers for prevention of secondary
complications (Howard, et al. 2006).
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When intravenous gammaglobulin became
available, the incidence of chronic enteroviral
infection has markedly decreased in
individuals with XLA.
As a result of earlier diagnosis, more liberal use
of antibiotics, and the development of
preparations of gammaglobulin that allow
normal concentrations of serum IgG to be
achieved, most individuals lead a normal life
and may live well into their fifties (Howard, et
al. 2006).
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Your results show that you have a genetic disease
called x-linked agammaglobulinemia. It primarily
affects boys that's why you and your brother are so
sick all the time .The disease causes you to be unable to
produce antibodies that make up gamma globulins in
your blood.
This inherited disease caused you to become very sick
since you were unable to fight off infections. Luckily,
we have medicine that can make you better and only
involves one shot every two to four weeks,Do you have
any questions?
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B cell precursor
Rearrangement
of Ig genes which is involved in signal
Btk is a protein expressed
in B cell development
transduction and is involved in signaling the development of B cells if they
are able to transiently express
the heavy chain and light chain in the cell.
Immature B cell
A defect in Btk would cause
B cell development
to be incomplete and
Negative
selection
stopped at the pre-B cell step
Without maturation, B cells are not differentiated or sent to the lymph nodes
Mature B cell
which results in the lack of tonsils
Migration to peripheral lymphoid organs
When B cells mature they become plasma cell and release antibodies which
have multiple functions
B cell neutralization, activating
Antibodies can be involved Activated
in opsonization,
complement and blocking bacteria from attaching to epithelial cells
Plasma Cell
Memory B cell
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The objective was to investigate whether or not the alterations in
the phagocytosis of monocytes in XLA patients was due to
number of complement and Fcg receptors
Patients with XLA, CVI and healthy patients’ monocytes were
analyzed by flow cytometry for complement receptors and Fcg
receptors
CVI is a disease which prevents B cell differentiation and ability to
produce antibodies but B cells are at normal levels
Found that XLA patients show the same or higher percentage of
monocytes expressing Fcɤ and CR receptors
Findings support idea the inefficient chemotaxis and phagocytosis
in XLA patients are not due to deficient receptors but rather
defects in cytoplasmic transduction mechanisms, a result of the
Btk defect
Critiques:
The sample size is small and
all patients are on
immunoglobulin therapy which
could possibly result in an
increase in expression of
receptors
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X-linked agamaglobulinemia results from a defect
in Btk which causes a signal transduction defect
that does not allow B cells to develop past the preB cell stage resulting in no antibody production
Typical symptoms are recurrent pyogenic
infections, ear infections, lung infections after
infancy(nursing), missing tonsils, missing
adenoids, pneumonia
No way to cure at this time, lifelong injection of
immunoglobulins
With the development of immunoglobulin therapy
it is possible to live a normal life
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Moschese, V., Orlandi, P., Di Matteo, G., Chini, L., Carsetti, R., Di Cesare,
S., et al. (2004). Insight into B cell development and differentiation. Acta
Paediatrica, 9348-51. Retrieved from Academic Search Premier database.
Amoras, A., da Silva, M., Zollner, R., Kanegane, H., Miyawaki, T., &
Vilela, M. (2007). Expression of Fcγ and complement receptors in
monocytes of X-linked agammaglobulinaemia and common variable
immunodeficiency patients. Clinical & Experimental Immunology, 150(3),
422-428. doi:10.1111/j.1365-2249.2007.03512.x.
Howard V, Greene JM, Pahwa S, Winkelstein JA, Boyle JM, Kocak M,
Conley ME. The health status and quality of life of adults with X-linked
agammaglobulinemia. Clin Immunol. 2006; 118: 201–8. [PubMed]