The cause of IgG subclass deficiency remains unknown. In a few cases, a partial gene deletion has been identified. Subclass deficiency may also be associated with IgA deficiency or ataxia-telangiectasia (inherited muscle disorder), and it may be more common in families who have a history of common variable immunodeficiency (CVID).
IgG subclass deficiencies usually occur in pairs. IgG1 often occurs with IgG3, and IgG2 often occurs with IgG4). Since IgG subclass deficiency impairs the immune system, recurrent infections are common among patients. These infections are usually caused by encapsulated (closed in a sheath) bacteria, such as Streptococcus pneumonia and Hemophilus influenzae, and they are especially common in patients who have IgG2 deficiency.
General: Many patients are asymptomatic (experience no symptoms), while others may suffer from recurrent ear infections, sinusitis, bronchitis and pneumonia. In rare cases, patients have experienced recurrent episodes of meningitis (infection of the membranes that cover the spinal cord and brain) or bacterial infections of the bloodstream.
Lung function impairment and bronchiectasis (widening and scaring of airways) have also been reported in some patients. Some patients develop autoimmunity (cells in the immune system mistake the body's own tissues for an invading substance).
IgG1 deficiency: Most patients have IgG1 deficiency also have low levels of other immunoglobulins. This condition is called common variable immunodeficiency (CVID).
IgG2 deficiency: IgG2 subclass deficiency, which occurs either as an isolated entity or in combination with IgG4 deficiency, is the most common subclass deficiency.
Some patients with IgG2 deficiency may be asymptomatic, which may be because the antibody response was shifted to another IgG subclass. Children with IgG2 and IgG4 deficiency who also have systemic lupus erythematosus (chronic inflammatory connective tissue disease) may present experience cardiac tamponade (compression of the heart) rather than more common signs of systemic lupus erythematosus (like nephropathy and arthritis).
This particular deficiency usually causes the highest frequency of infectious complications, especially in the respiratory tract (like bronchiectasis, bronchopneumonia, bronchitis, obstructive lung disease and asthma). This because the IgG2 antibodies play a vital role in the immune response to organisms with polysaccharide capsules (like H. influenzae type B).
In addition, IgG2 deficient patients may be unable to produce specific antibodies after receiving certain vaccines, including the pneumococcal or the Hemophilus influenzae vaccines.
IgG3 deficiency: IgG3 deficiency, which may occur with IgG1 deficiency, has been associated with recurrent upper and lower respiratory tract infections. IgG3 may play an important role in the primary immune response to viral respiratory agents. Also, IgG3 is the predominant antibody response to the Moraxella catarrhalis bacteria, which is commonly found in patients who have chronic sinusitis.
IgG4 deficiency: IgG4 deficiency occurs in 10-15% of the general population. Researchers have described selective IgG4 deficiency in patients who have severe recurrent respiratory tract infections and bronchiectasis.
When IgG deficiency occurs with low levels of both IgG4 and IgA, it is usually associated with ataxia-telangiectasia.
General: The standard diagnostic test for IgG subclass deficiency is an enzyme-linked immunosorbent assay (ELISA) or a radial immunodiffusion test. Test results may vary from one laboratory to another. A healthcare provider should also evaluate the patient's response to vaccines. Patients who have IgG2 subclass deficiency often have poor responses to the Pneumococcal vaccine.
Enzyme-linked immunosorbent assay (ELISA): An enzyme-linked immunosorbent assay is a rapid test where an antibody or antigen is linked to an enzyme in order to detect a match between an antibody and antigen. If the target substance is present in the blood sample, the test solution will have an intense color reaction that is caused by the attached enzyme.
Radial immunodiffusion: A radial immunodiffusion test measures the amount of serum proteins in the blood.
Blood test: The amount of active binding antibodies in the blood can be determined by measuring the levels of antibodies to various vaccines (like diphtheria, tetanus, measles or pneumococci). Patients who have IgG2 subclass deficiency are often unable to produce specific antibodies after receiving the Pneumococcal vaccine.