Incidence

The incidence of this fairly common primary immune disorder is not yet known. However, no epidemiological studies have been conducted to determine its prevalence in any defined population.

Disease Description

IgG Subclass Deficiency occurs when there is an imbalance of the IgG subclasses with one or more subclasses being deficient. The overall level of IgG can be normal, but individual subclass levels may be higher or lower than normal.

These individuals may have increased susceptibility to infection and have a history of frequent bacterial and viral infections since childhood, low or normal serum gammaglobulin levels, and selective deficiencies of IgG subclasses 1, 2, 3, or 4. However, there are many cases of IgG deficiency in healthy individuals.

The cause of IgG Subclass Deficiency is generally unknown. A few cases arising from a partial gene deletion have been identified. Subclass deficiency may be associated with IgA deficiency, or ataxia-telangiectasia (irregularities or failure of muscle coordination affecting the eyes and skin; frequent respiratory infections and immunodeficiency, re. Louis Bar Syndrome), and may be more common in families where Common Variable immunodeficiency is found.

Clinical Signs and Symptoms

Patients with clinical symptoms usually present with a history of frequent infections involving the respiratory tract such as otitis media (ear infection), sinusitis , bronchitis, or pneumonia. The causes of these infections are often found to be encapsulated (closed in a sheath) bacteria such as Hemophilus influenzae and Streptococcus pneumonia , especially in the case of an IgG2 deficiency. Lung function impairment and bronchiectasis (widening and scaring of airways) also have been reported in some patients. Some patients develop autoimmunity (immunity to the body's own tissues). Clinical presentation of these patients appears to vary according to the type of IgG Subclass deficiency which is present.

IgG2 deficient patients may have a poor response to some vaccines, such as the pneumococcal or the Hemophilus influenzae vaccines.

Since infants have little IgG at birth and the amount of IgG increases over the first few years of life to approach adult levels at about age 2, it is logical that the levels of the IgG subclass increase also. But this happens at a different rate for each child, thus, for infants and children, the "normal" range for IgG subclasses is very broad. A young child of one or two can have lower than normal levels of one or more IgG subclasses, but then later have entirely normal levels. IgG2 deficiency is the most common subclass deficiency in early childhood while IgG3 deficiency is the most common in adults.

While a deficiency of one subclass may be noted, this does not necessarily mean that a biologically important defect is present. What is important is that enough active binding antibody is found in the blood. This can be determined by measuring the levels of antibody to various vaccine agents (diphtheria, tetanus, measles, pneumococci, etc.) and by purposefully immunizing to determine how much response is made. Another issue is that IgG Subclass values may vary from laboratory to laboratory and deficiency of a given subclass may not correlate with clinical disease.

Various minor abnormalities of B- and T- lymphocyte level and function also have been reported.

Diagnosis

The method of choice for diagnosing IgG Subclass Deficiency is radial immunodiffusion, ELISA, radioimmune assays, or other methods. Test results also vary from one laboratory to another despite careful control of reagents and methodology, and no uniform methods are established. Most important is determining response to vaccines; if a person with an IgG2 subclass defect has a poor response to pneumococcal vaccine, a true antibody defect is present.

Treatment

Gammaglobulin prophylaxis has been shown in some studies to reduce the number of infections and courses of antibiotics for patients who have substantial IgG2 Subclass Deficiency and poor response to bacterial vaccines. Dosages range from 200 to 400 mg/kg, given once every 3 or 4 weeks. Unless a clear deficit of antibody is documented (by measuring the amounts of antibody in the blood before and after vaccination, for example), it is doubtful that immunoglobulin treatment is warranted.

Prognosis

Unknown.

Prevention

Unknown.

Back to