Agammaglobulinemia is an inherited disorder in which a person has very low levels of protective immune system proteins called immunoglobulins. Immunoglobulins are a type of antibody. Low levels of these antibodies make you more likely to get infections. It is also known as hypogammaglobulinemia.

CAUSES

Agammaglobulinemia is inherited. It is a rare disorder that mainly affects males. It is caused by a gene defect that blocks the growth of normal, mature immune cells called B lymphocytes. As a result, the body makes very fewer immunoglobulins. Immunoglobulins play a major role in the immune response, which protects against illness and infection. Common infections include ones that are due to bacteria such as Haemophilus influenza, pneumococci (Streptococcus pneumonia), and staphylococci. Common sites of infection include:

  • Gastrointestinal tract
  • Joints
  • Lungs
  • Skin
  • Upper Respiratory Tract

PATHOPHYSIOLOGY

In the fetal bone marrow, the first committed cell in B-cell development is the early pro-B cell. These cells develop into late pro–B cells in which rearrangement of the heavy chain genes occurs. When the heavy chain is produced, it is transported to the cell surface. Progression from this late pro–B-cell to the pre–B-cell stage involves the rearrangement and joining of the various segments of the heavy chain genes. The completion of rearrangement of the light and heavy chains and the presence of surface IgM results in the immature B cell, which then leaves the bone marrow.

Increasing expression of IgD in the transitional cells finally results in the mature B cell with IgM and IgD both expressed on their cell surface. The mature B cells circulate between secondary lymphoid organs and migrate into lymphoid follicles of the spleen and lymph nodes in response to further stimuli and various chemokines. T cells stimulate B cells to undergo further proliferation and Ig class switching, leading to the expression of the various isotypes IgG, IgA, or immunoglobulin E (IgE).

Agammaglobulinemia
Early stages of B-cell differentiation can be identified by the status of the immunoglobulin genes and by the cell surface markers CD34, CD19, and surface immunoglobulin

Mutations on Btk components of the pre–B-cell and B-cell receptor (lambdα5, Ig-α, and Ig-β), or the scaffolding protein BLNK account for approximately 90% of defects in early B-cell development.Mutations in Btk result in Bruton agammaglobulinemia.

SIGNS AND SYMPTOMS

  • Bronchitis 
  • Chronic diarrhoea
  • Conjunctivitis 
  • Otitis media 
  • Pneumonia 
  • Sinusitis 
  • Skin infections
  • Upper respiratory tract infections

COMPLICATIONS

  • Arthritis
  • Chronic sinus
  • Eczema
  • Intestinal malabsorption syndromes

TREATMENT

  • Antibiotics are often needed to treat bacterial infections.
  • Immunoglobulins are given through a vein or by injection to boost the immune system.
  • A bone marrow transplant may be considered.

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