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 |
|Patients * ||1175 ||28% ||17% ||13% ||9%|
|Healthy individuals ||162 ||8%||3%||1%||1%|
4.3IgG 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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