Immune Deficiency due to IgG subclass

If you are suffering from chronic Fatigue, chronic pain, Fibromyalgia, recurrent infections, allergies they you may have IgG or IgG subclass deficiency. If you have IgG subclass deficiency then vaccination can induce autoimmune disease in you. Certain immunodeficiencies are relatively simple to diagnose, being marked by grossly reduced serum levels of one or more classes of immunoglobulin. Other immunodeficiencies are less obvious and consequently more difficult to diagnose. The challenge is to accomplish the diagnosis and institute the appropriate treatment before permanent damage results. Immunoglobulin G (IgG) accounts for 70-75% of the total immunoglobulin pool in normal human serum. Unlike other immunoglobulins, IgG is not a single molecule but is composed of four distinct subclasses (IgG1, 2, 3 and 4), each having different functions. There is a wide variety of respiratory problems associated with IgG subclass deficiency, including recurrent otitis media, sinusitis, pneumonia, chronic obstructive airway disease, bronchiectasis and asthma. The way to test them is by getting a IgG subclass screen in your blood.   IgG 1 is the most abundant of the four subclasses and reaches 'adult' levels in early childhood. IgG1 provides the largest immune response and the dominant response to protein/polypeptide antigens. IgG2 is the most common IgG subclass deficiency and may also be associated with IgA deficiency. Recurrent respiratory infections in children (Haemophilus influenzae type b, Streptococcus pneumoniae) are particularly associated with IgG2 deficiency. 'Adult' levels of IgG2 are not usually reached until 6-7 years of age. IgG3 deficiency can manifest itself in recurrent respiratory infections with obstructive lung disease. It may be seen in association with IgG1 deficiency. Usually patients suffering from Chronic Fatigue Syndrome and Fibromyalgia will have low IgG3 deficiency. IgG4 deficiency may be associated with IgG2 and IgA deficiency in ataxia telangiectasia, frequently masked by normal levels of total IgG. Subclass deficiencies can also be associated with T-cell dysfunction. Elevated levels of IgG4 are seen in atopic dermatitis, asthma and some parasitic diseases. In a recent study of 56 adults with IgA deficiency the authors found the susceptibility respiratory tract infections was not related to the degree of IgA deficiency but was related to the deficiency of IgG4.

 

 Causes of subclass Deficiencies and complete deficiency of individual IgG subclasses may have several consequences:

IgG1: IgG1 deficiencies often result in a decreased level of total IgG (hypogammaglobulinemia). A deficiency of this quantitatively most important subclass is often associated with recurrent infections and might occur in combination with (individual) deficiencies of other subclasses, e.g. IgG3 (36,64). In a recent evaluation of IgG1 concentrations in adults (n=1175) with suspected IgG subclass abnormalities, decreased IgG1 level were observed in 28% of the individuals (table IV).
Read reported IgG1 subclass deficiencies in patients with chronic fatigue syndrome, whereas all other immunoglobulin isotypes were normal (65).
IgG1 deficiency is often associated with Common Variable ImmunoDeficiency.

IgG2: An IgG2 deficiency is often associated with otitis media acute and sinusitis, association with ataxia telangietasia and with System Lupus Erythematosus (SLE) has also been reported.
In about half of all IgG subclass deficiencies the IgG2 concentrations are decreased. An isolated IgG2 deficiency is associated with decreased responses to infections with encapsulated bacteria and after immunisation with polysaccharide antigens (38,66). These patients show recurrent respiratory tract infections with pneumococci and/or Haemophilus influenza type B (67,68,69). Low concentrations of IgG2 often occur in association with a deficiency in IgG4 and IgA.

IgG3: Along with IgG1, the IgG3 subclass is most frequently present in the antibody response to protein antigens. IgG3 deficiency has been associated with a history of recurrent infectious, leading to chronic lung disease. Decreased IgG3 levels are frequently associated with IgG1 deficiency (63).

IgG4: An IgG4 deficiency is difficult to assess. In healthy children, IgG4 may have very low concentrations. Methods that are used to measure IgG4 levels have not always been sensitive enough to distinguish complete absence of IgG4 from low-normal IgG4 levels. Thus, in most studies the assessment of IgG4 deficiency is hampered by the high frequency of undetectable IgG4 levels, which is especially common in young children. Although several studies have shown that a large population of patients with recurrent respiratory tract infection have low IgG4 concentrations, the significance of this finding is not clear since a low concentration of IgG4 also occurs in a substantial percentage of healthy children (63,70).

TABLE IV Frequency (%) of decreased IgG subclass concentrations in adults

Sample Origin	Number of samples	IgG1	IgG2	IgG3	IgG4
Children	3854	4.9%	19.4%	6.3%	0.8%
Patients *	1175	28%	17%	13%	9%
Healthy individuals	162	8%	3%	1%	1%

 

4.3 IgG subclasses and allergy (85,86,87)

Among allergen-specific IgG antibodies in allergic individuals, there is a preponderance of IgG1 and IgG4, while IgG2 and IgG3 responses are small. Other findings in allergic patients include the following:

-Elevated IgG4 concentrations often occur in sera of patients with atopic eczema and dermatitis, probably as the result of prolonged antigenic stimulation (88).

-In allergy to many different allergens, allergen-specific IgG antibodies are predominantly of the IgG4 subclass and their levels increase during desensitisation therapy. In the antibody response to desensitization/immunotherapy, initially mainly IgG1 is formed, whereas IgG4 becomes more prominent after 1-2 years.

 

 

 

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