Immunoglobulins (Ig) are glycoprotein molecules that function as antibodies. Since antibodies are present in the bloodstream or bound to cell membranes, they are considered part of the humoral immune system. The humoral system is mediated by secreted antibodies.
Immunoglobulin G (IgG) antibodies are the smallest, but most abundant antibodies in the body, making up 75-80% of all the antibodies in the body. They are present in all body fluids. The IgG antibodies are considered the most important antibodies for fighting against bacterial and viral infections, and they are the only antibodies that can cross the placenta during pregnancy.
IgG isotypes are associated with complement fixation (immune response in which an antigen-antibody combination inactivates a complement) opsonization (process by which antigens are altered so that they are more efficiently engulfed and destroyed by immune cells), fixation to macrophages and membrane transport.
There are four subclasses of the IgG class of antibodies -
IgG1, IgG2, IgG3 and IgG4. As the antibody-producing B-cell matures, it can switch from one subclass to another.
In healthy individuals 60-70% of IgG antibodies in the bloodstream are IgG1, 20-30% are IgG2, 5-8% are IgG3 and 1-3% are IgG4. The levels of IgG subclasses in the bloodstream vary with age. IgG1 and IgG3 reach normal adult levels when an individual is about five to seven years old, while IgG2 and IgG4 levels rise more slowly, reaching adult levels at about 10 years of age. In young children, the ability to make antibodies to bacteria (typically antibodies of the IgG2 subclass) develops more slowly than the ability to make antibodies to proteins.
IgG subclass deficiencies occur when the B-cells do not mature properly, and they are unable to switch IgG subclasses. This causes 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. IgG2 deficiency is the most common subclass deficiency in early childhood, while IgG3 deficiency is the most common in adults.
Individuals who have IgG subclass deficiency may have increased susceptibility to infections, such as ear infections, sinusitis, bronchitis and pneumonia.
The incidence of IgG subclass deficiency remains unknown. No epidemiological studies have been performed to determine its prevalence in any specific population.
The prognosis for patients with IgG subclass deficiency is generally good. Many children appear to outgrow their deficiencies once they reach adulthood. While there is currently no cure for IgG subclass deficiency, treatment can help prevent infections commonly associated with the disorder. For those patients who experience persistent deficiencies, antibiotics, immunizations and gammaglobulin replacement therapy may help prevent serious infections and the development of impaired lung function, hearing loss or other injuries caused by infections.
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.
General: Many patients outgrow their deficiency once they reach adulthood. For those patients who experience persistent deficiencies, antibiotics, gammaglobulin replacement therapy and immunizations may help prevent serious infections and the development of impaired lung function, hearing loss or other injuries caused by infections.
Antibiotics: Antibiotics are used to treat bacterial infections that are commonly associated with IgG subclass deficiency. Different antibiotics will be prescribed for different lengths of time, depending on the type and severity of the infection.
Gammaglobulin therapy: Gammaglobulin prophylaxis (preventative treatment) has been shown in some studies to reduce the number of infections and courses of antibiotics in patients who have substantial IgG subclass deficiencies. Dosages range from 200 to 400mg/kg, given once every three or four weeks.
It is recommended that trough immunoglobulin levels be monitored regularly to help define the optimal time between doses since immunoglobulin clearance varies among individuals. Patients should maintain trough levels at 400-500mg/dL during therapy.
Although the benefits of gammaglobulin therapy are significant, some patients may experience side effects. About 3-12% of patients who receive gammaglobulin therapy develop headache, myalgia (muscle pain), chills, fever and mild nausea upon infusion. If symptoms are intolerable, the infusion rate may be decreased to 0.01mL/kg/min to reduce side effects. In addition, side effects can also be minimized with antihistamines, acetaminophen and/or hydrocortisone.
Immunizations: Vaccination is recommended in patients who do not have antibodies to Pneumococcus and Haemophilus polysaccharides, regardless of whether they have a IgG2 subclass deficiency. If the patient does not respond to Pneumococcus and Haemophilus polysaccharide vaccines, they may be revaccinated with protein-conjugated Pneumococcus and Haemophilus polysaccharide vaccines.
Zinc: Zinc appears to be an essential trace element for the immune system, but research on the effect of zinc supplementation on immune function is scant and mostly focuses on patients with specific diseases. Zinc gluconate appears to exert beneficial effects on immune cells, improving CD3 and CD4 counts and increasing CD4/CD8 ratios in children. There are relatively few studies that examine zinc levels and the effects of zinc supplementation on the health of the elderly population. Further research is needed before a recommendation can be made.
Zinc is regarded as a relatively safe and generally well-tolerated therapy, when taken at recommended doses, and few studies report side effects. The recommended daily dose for adult and teenage males is 15mg. The recommended daily dose for adult and teenage females is 12mg. The recommended daily dose for pregnant females is 15mg and 16-19mg for breastfeeding females. The recommended daily dose for children ages 4-10 is 10mg, and 5-10mg for children 0-3 years old.
Arginine: Preliminary study results suggest that arginine supplementation may enhance the immune response elicited by the pneumococcal vaccine in older people. More studies are needed to confirm these results.
Astragalus: Astragalus has been suggested as an immune system stimulant in preliminary laboratory and animal research, and in traditional accounts. Reliable human studies are lacking. High-quality human research is necessary before a firm conclusion can be drawn.
Beta-carotene: Preliminary research of beta-carotene for immune system maintenance or stimulation shows mixed results. Further research is needed before a conclusion can be drawn.
Cat's claw: A few early studies suggest that cat's claw may boost the immune system. However, results from different studies are conflicting. Therefore, there is not enough information to recommend cat's claw for this use.
Copper: Copper is involved in the development of immune cells and immune function in the body. Severe copper deficiency appears to have adverse effects on immune function, although the exact mechanism is not clear.
Echinacea: Echinacea has been studied alone and in combination preparations for immune system stimulation. It remains unclear if there are clinically significant benefits. Additional studies are needed in this area before conclusions can be drawn regarding safety or effectiveness.
Gamma linolenic acid (GLA): Few clinical trials have investigated the effect of GLA on immune responses in healthy human subjects. Results from one randomized, clinical trial suggest that GLA, as blackcurrant seed oil may offer some benefits. Further, well-designed clinical trials are required before definite conclusions can be made.
Ginseng: A small number of studies report that ginseng may stimulate activity of immune cells in the body, improve the effectiveness of antibiotics in people with acute bronchitis and enhance the body's response to influenza vaccines. Additional studies are necessary before a clear conclusion can be reached.
Goldenseal: Goldenseal has been suggested to be an immune system stimulant. However, there is little human or laboratory evidence in this area. More research is needed before a firm conclusion can be drawn.
Maitake mushroom: Animal and laboratory studies suggest that beta-glucan extracts from maitake may alter the immune system. However, no reliable studies in humans are available.
Massage: Preliminary evidence suggests massage therapy may preserve immune function. Further research is needed before a firm conclusion can be made.
Meditation: Preliminary research reports increased antibody response after meditation. Further study is needed to confirm these findings.
Mistletoe: A few small trials found mistletoe to be promising as an immunostimulant in individuals with the common cold. Further studies are needed to confirm these results.
Probiotics: Lactobacillus in fermented milk, low-fat milk or lactose-hydrolyzed low-fat milk may enhance immune function. Bifidobacterium may also enhance immune function. However, commercially produced yogurt may not yield similar benefits. There is some evidence that probiotics added during food preparation (e.g., waffles with Enterococcus faecium M-74 added) can enhance immune functioning. More studies are needed, particularly with yogurt, to give concrete recommendations.
Vitamin A (retinal): Vitamin A deficiency may compromise immunity, but there is no clear evidence that additional vitamin A supplementation is beneficial for immune function in patients who are not vitamin A deficient.
Vitamin B6 (pyridoxine): Vitamin B6 is important for immune system function in older individuals. One study found that the amount of vitamin B6 required to reverse immune system impairments in elderly people was more than the current recommended dietary allowance (RDA). Well-designed clinical trials on vitamin B6 supplementation for this indication are needed before a recommendation can be made.
Vitamin E: Studies of the effects of vitamin E supplementation on immune system function have yielded mixed results. Further research is needed before a clear conclusion can be drawn.
DHEA (dehydroepiandrosterone): Some textbooks and review articles have suggested that DHEA can stimulate the immune system. However, current scientific evidence does not support this claim.
Lycopene: It has been proposed that lycopene and other carotenoids, such as beta-carotene, may stimulate the immune system. However, several studies of lycopene supplements and tomato juice intake in humans report no effects on the immune system.
Currently, there is no known method of prevention for IgG subclass deficiency.
This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).
- Genetics Home Reference. Immunoglobulin G (IgG). http://ghr.nlm.nih.gov/. Accessed March 17, 2007.
- National Primary Immunodeficiency Resource Center. IgG Subclass Deficiency. http://www.info4pi.org/ . Accessed March 17, 2007.
- Natural Standard: The Authority on Integrative Medicine. http://www.naturalstandard.com. Copyright © 2007. Accessed March 17, 2007.
- Tulane University. Immunoglobulin Structure. 10/11/00 View Article. Accessed March 17, 2007.
Copyright © 2011 Natural Standard (www.naturalstandard.com)