rev:February 3, 1997
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4.4 IgG subclasses in other diseases
Decreased or increased levels of IgG subclasses in serum are associated with
several other diseases, examples of which will be given here (90).
4.4.1 Infectious diseases (6)
In most infections the first antibodies to appear will be of the IgM class, while those of the IgG class will be produced later. In general, microbial protein antigens will mainly evoke antibody responses of the IgG1 and IgG3 subclasses, with a minor contribution of IgG2 and IgG4. On the other hand, polysaccharide antigenswill predominantly induce IgG2 antibodies.
Some disease-specific observations:
-Pneumococcal otitis media in children is associated with a decreased level of IgG2.
-Patients with recurrent infections by encapsulated bacteria often show decreased levels of IgG2 and IgG4.
-Recurrent respiratory infections with bronchiectasis are often associated with decreased levels of IgG2,IgG3 and IgG4.
-Cystic fibrosis with chronic Pseudomonas aeruginosa infection is associated with an increased level of IgG2 and IgG3, the latter of which seems to be of prognostic significance.
4.4.2 Autoimmunity
In autoimmune diseases the levels of IgG subclasses do mostly not differ
from those in healthy individuals, but specific autoantibodies show variable
subclass restrictions: frequently, autoantibodies are of the IgG1 and IgG3
subclasses (91,92).
-Human rheumatoid factors (RF) are defined as IgG,IgA or IgM antibodies against
the Fc fragment of immunoglobulin. In most cases, RF have been found to bind
to the Fc fragments of IgG.As for their subclass specificity, most RF have
been shown to react with IgG1,followed by IgG2 and IgG4. Binding of RF to
IgG3 is rare.
-Abnormal IgG1: IgG2 ratios have been reported in patients suffering from
connective tissue diseases. In case of a selective polyclonal increase of
IgG1, one should be alert for the possibility of Sjogren's syndrome. It has
been suggested that this immunoglobulin abnormality is the product of a
restricted oligoclonal B cell response and may thus be the consequence of
a benign B cell lymphoma (93,94,95,96).
-Autoantibodies to neutrophil cytoplasmic antigens (ANCA) are predominantly of the IgG1 and IgG4 subclass (97,98). Autoantibodies of the IgG3 subclass almost exclusively occur in patients with renal involvement(98).
4.4.3 Haemolytic disease of the
newborn
Antibodies to blood group antigens show a more or less IgG subblass-distinct profile. The influence of anti-Rh(D) IgG subclasses on the severity of haemolytic disease of the newborn has been examined by many groups (99,100,101,102). In the majority of samples tested, both IgG1 and IgG3 antibodies were detected and the haemolytic disease was more severe than when only IgG1 was present. The significance of IgG3 antibodies to controversial. Some authors have suggested that IgG3 is always associated with overt haemolysis, but others could not confirm this. Blood group antibodies of the IgG4 subclass, in contrast to those of IgG1, IgG2 and IgG3 subclasses, are known not to cause clinical problems (haemolysis), which finding is mainly explained by the inability of such antibodies to activate complement(22,103,104,105).The determination of IgG subclasses is indicated especially when there is a clear discrepancy between serological findings and signs of increased red cell destruction in vivo (106).
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