Hypogammaglobulinemia

by Dr. Saul Greenberg

What is it?

Hypogammaglobulinemia is a disorder that is caused by a lack of B-lymphocytes and a resulting low level of immunglobulins (antibodies) in the blood. Immunoglobulins play a dual role in the immune response by recognizing foreign antigens and triggering a biological response that culminates in the elimination of the antigen. Antibody deficiency is associated with recurrent infections with specific types of bacteria. In pure B-cell disorders, cellular immunity generally is intact and the frequency of viral, fungal, and mycobacterial (e.g. tuberculosis) infections is not increased. There are 5 major types of immunoglobulins: immunoglobulin G, immunoglobulin M (IgM), immunoglobulin A (IgA), immunoglobulin D (IgD), and immunoglobulin E (IgE).

The most common congenital abnormalities of B lymphocyte production include:

Hypogammaglobulinemia (Common Variable Immunodeficiency)
Ig A Deficiency
X-linked Agammaglobulinemia (Bruton Disease)
Transient hypogammaglobulinemia of infancy

Hypogammaglobulinemia or Common Variable Immunodeficiency (CVID)

CVID is the second most common cause of hypogammaglobulinemia and affects both sexes equally. The incidence is about 1 in 50,000 people. In most patients there is a reduced amount of the immunoglobulins IgG, IgA, and IgM in the blood. It is an immune deficiency disorder that can be acquired or inherited. In most cases, there is no family history of immunodeficiency. However, in instances where more than one family member is affected, an autosomal recessive (two abnormal genes, one from each parent) mode of inheritance is suggested. In about 5% of the cases, one or more of the family members can be found to be IgA deficient.

Selective IgA deficiency

IgA deficiency is the most common antibody deficiency syndrome, about 1 case in 700 persons. Recurrent infections may occur in as many as 50% of IgA-deficient patients, but most of these individuals are healthy. Some patients develop symptoms after an uneventful childhood and early adulthood. Recurrent or chronic upper and lower respiratory tract infections is common as is Giardia lamblia infections of the gastrointestinal tract. Patients with undetectable levels of IgA antibodies may develop severe allergic reactions if they receive blood products

X-linked agammaglobulinemia (XLA)

Symptoms in Bruton disease begin at age 7-9 months, after a significant decline of maternal antibodies. The disorder affects boys only and is characterized by recurrent bacterial infections during the second half of the first year of life. Chronic otitis media, sinusitis, and pneumonia are the most common infections. Patients often have undersized or scanty tonsils and lymph nodes. 15% of patients with XLA die of infectious complications by age 20 years.

Transient hypogammaglobulinemia of infancy (THI)

THI is related to a delayed onset of immunoglobulin production in infants. These patients recover and develop a normal antibody response when aged 2-3 years. During their first years, these patients have a high incidence of recurrent upper respiratory infections but not of pneumonias or life-threatening infections. These patients do not require IVIG therapy (see below).

What are some of the symptoms?

Patients with B-cell deficiencies begin having bacterial infections when aged 7-9 months, when the placental antibodies fall to undetectable levels.Symptoms are related to the severity of the immunodeficency, which may include the following:

Respiratory infections

Paranasal sinusitis, bronchitis, chronic cough
Chronic otitis media (ear infection)
Development into more serious respiratory conditions

Chronic lung disease
Pneumonia
Chronic bronchiectasis
Interstitial emphysema

Gastrointestinal disorders

Chronic diarrhea, weight loss and malabsorption of food secondary to Giardia Lamblia infection

Autoimmune disease - Rheumatoid arthritis, vitiligo, hemolytic anemia,
thrombocytopenia, and neutropenia
Malignancy – risk of certain malignancies is high
Growth retardation in those with early-onset recurrent infections

How is it diagnosed?
Some tests that indicate hypogammaglobulinemia include:

Low serum immunoglobulins and B lymphocytes
Missing specific antibodies to any vaccines the child has received
Absence of antibodies to A and B blood group antigens

How is it treated?

Hypogammaglobulinemia is frequently treated with intravenous gammaglobulin (IVIG), given every three to four weeks intravenously or subcutaneously. Antimicrobial therapy should be initiated at the first sign of infection. Patients with chronic sinusitis or lung disease may need long term treatment with broad spectrum antibiotics. . Physical therapy and daily postural draining of secretions and pus from lungs and bronchi may be necessary for those who have developed bronchiectasis. For those patients suffering gastrointestinal problems or malabsorption problems, evaluation for Giardia lamblia, rotavirus, or other infections should be undertaken. In most patients with immunodeficiency and arthritis who have never received gammaglobulin, adequate treatment with gammaglobulin usually provides symptom relief.

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