X-Linked
Agammaglobulinemia (XLA)
1.
Contents
- Definition
- B-Cell
Maturation
- Clinical
Presentation
- Diagnosis
- Treatment
& Prevention
- Latest
Citations
2. Definition
- First
desrcribed in 1952 by Dr Ogden Bruton
-Bruton's Agammaglobulinemia
-Congenital Agammaglobulinemia
- Inherited
immunodeficiency male disease in which patients lack the ability
to produce
-Antibodies
-Proteins that make up gamma globulin
-Immunoglobulin fraction of blood plasma
- Affected
males
Few or no B cells ā lymph nodes are very small & No tonsils
and cervical lymph nodes
- Serum
Usually no IgA, IgM, IgD, or IgE; small amounts of IgG from
placenta
- First
6-12 months
Protection by maternal IgG from placenta to fetus
- As
IgG is exhausted
Males develop recurrent pyogenic infections
3. B-Cell Maturation
- XLA
patientsāB-lymphocyte precursors, but very few undergo maturation
- Failure
of B-lymphocyte precursors to mature into B-cells and ultimately
plasma cells
- Mutations
in the BTK (90%) ā B-cell Cytoplasmic (or Bruton's) Tyrosine
Kinase gene (1993)
- Necessary
for the maturation of B-lymphocyte
- On
the long arm(q) of X-chromosome
- Facilitates
the prenatal diagnosis
- Infections
of mucus membranes
- Middle
ear (Otitis)
- Sinuses
(Sinusitis)
- Lungs
(Conjuctivitis)
- Nose
(Rhinitis)
- Lungs
(Pneumonia)
- Joints
(Arthritis)
- Blood
stream of internal organsāSpread
- Most
common infectious bacteria
- Streptococcus
- Pneumococcus
- Staphylococcus
5.
Diagnosis
- Immunoelectrophoresis
ā The levels of IgM, IgG, and IgG in infant's blood serum
- Response
to specific Abs āTetanus & Diphteria (Killed vaccines)
- Absence
of B-cells (CD19+ cells<1%)
- SSCP
analysis of BTK gene for mutations for prenatal diagnosis
- Family
history
- BTK
mutations ā X-linked autosomal recessive
6.
Treatment & Prevention
- Commercially
prepared gamma globulins (Gamimune or Gammagard)
- Intravenously
injected immunoglobulins
- Avoid
crowds and people with active infections
- Genetic
counseling for parents of XLA patient for more children
7.
Latest News about XLA
Long-lasting
memory-resting and memory-effector CD4+ T cells in human
X-linked agammaglobulinemia
Conflicting results obtained from animal
studies suggest that B cells play a role in maintaining
long-term T-cell memory and in skewing T-cell response
toward a T-helper 2 (T(H)2) phenotype. X-linked agammaglobulinemia
(XLA) is a genetic human disease characterized by the
lack of circulating B cells due to the mutation of Bruton
tyrosine kinase. This disease thus represents a unique
model for studying the role of B lymphocytes in regulating
T-cell functions in humans. To this aim, we analyzed hepatitis
B envelope antigen (HBenvAg)-specific T-cell memory in
a series of XLA patients vaccinated against hepatitis
B virus (HBV).
We found HBenvAg-specific T lymphocytes
producing interferon-gamma, interleukin-4, or both in
the peripheral blood of XLA patients up to at least 24
months after completing the standard anti-HBV immunization
protocol. The HBenvAg-specific T-cell frequencies and
the percentage of patients with these responses were not
significantly different from healthy vaccinated controls.
By combining cell purification and enzyme-linked immunospot
assay, we found that effector CD27- T cells, which promptly
produced cytokines in response to antigen (Ag), and memory-resting
CD27+ T cells, which required Ag restimulation to perform
their functions, were maintained in both XLA patients
and controls for up to 24 months after the last vaccination
boost.
These data strongly suggest that B cells
are not an absolute requirement for the generation of
effective T-cell memory in humans, nor do they seem to
influence T(H)1/T(H)2 balance.
Paroli M, Accapezzato D, Francavilla V, Insalaco A,
Plebani A, Balsano F, Barnaba V. Blood 2003
Mar 15;99(6):2131-7
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