Bruton's agammaglobulinemia

Bruton's agammaglobulinemia (X-linked agammaglobulinemia, X-linked hypogammaglobulinemia, XLA, OMIM: : 300755) was the first described genetic immunodeficiency (described by Brutonon in 1952). It belongs to antibody immunodeficiencies.

Etiology and pathogenesis
The protein kinase BTK (Bruton tyrosine kinase), which is expressed in large quantities in B-lymphocytes  precursors. Under normal conditions, B-lymphocyte development first involves the rearrangement of genes for the immunoglobulin heavy chain, follwed by the rearrangement of genes for the light chain. It turns out that if BTK is mutated, development ends with rearrangement of the immunoglobulin heavy chain gene. Light chains are not synthesized and immunoglobulin molecules cannot be assembled. BTK kinase is responsible for biosignal transmission from B-lymphocyte receptors (and their precursors) to effector mechanisms.

The critical section in this disease is part of the long arm of the X chromosome – Xq21.3-q22. Thus, as a GR hereditary disease, it occurs much more often in boys.

Clinical Picture
The disease begins to fully manifest itself only after the 6th month of age because until then the newborn is at least partially protected by maternal immunoglobulins. Manifestations mainly include repeated bacterial infections of the respiratory system (bronchitis, otitis, pharyngitis, sinusitis...); the pathogens involved are almost always Haemophilus influenzae, Streptococcus pneumoniae, or Staphylococcus aureus. There is also a high susceptibility to viral infections, caused by, for example, enteroviruses (polioviruses, echoviruses, coxsackieviruses). A classic finding is a clear reduction (or complete absence) of B-lymphocytes, plasma cells and all immunoglobulin classes in peripheral blood. T-lymphocyte levels are normal or elevated.

There are different allelic variants; in some cases, an association with other manifestations, such as deafness, growth hormone deficiency or various neurological disorders, is described.

Therapy
Treatment includes immunoglobulin replacement therapy, and possibly prophylactic administration of antibiotics or antivirals.

Related articles

 * Primary immunodeficiency
 * Autosomally inherited agammaglobulinemia
 * Antibody

Source

 * ŠIPEK, Antonín. Genetically determined disorders of the immune system  [online]. Last revision 9/6/2006, [cit. 5/12/2009]. < http://www.genetika-biologie.cz/primarni-immunodeficiency >.