IgG Subclasses

Clinical use:
Isolated or compound deficiencies of all four subclasses have been described but, whilst some patients with deficiency exhibit clinical symptoms, others demonstrate no evidence of disease. With the exception of IgG1 deficiency, the total serum IgG is usually within the age-related reference range, or even increased,in both primary and secondary forms of IgG subclass deficiency. This suggests that the other subclasses may attempt to compensate for an isolated defect. IgG subclass assay may be of value in patients with multiple recurrent infections in whom there is no overt immunoglobulin deficiency. The total lack of an IgG subclass may be seen in healthy individuals.
IgG2 deficiency is the main form of IgG subclass defect seen amongst children, whilst after puberty IgG3 subclass defect becomes more common. IgG1 deficiency occurs most commonly in combination with defects in synthesis of other immunoglobulin isotypes and probably represents a form of common variable immunodeficiency.

IgG2 deficiency is the most common of the subclass deficiencies with an incidence approaching 1:1000. It may be associated with IgA deficiency, and it is in this situation that IgA deficient patients may benefit from replacement immunoglobulin therapy. It has been reported in association with systemic lupus erythematosus and juvenile diabetes mellitus. IgG2 deficiency has also been reported in children with multiple recurrent otitis media.

Combined IgG2 and IgG4 deficiency may be associated with ataxia telangiectasia. IgG1 concentrations are usually raised, thus masking the deficiency and giving normal total IgG concentrations. In the absence of compensatory IgG1 increases the combined deficiency is associated with severe pyogenic infections. There is some suggestion that IgG2-IgG4 deficiency may be a contributing factor in 10% of cases of ‘idiopathic’ bronchiectasis. IgG2-IgG4 deficiency may also be associated with IgA and/or IgE deficiency.

IgG3 deficiency is not usually associated with severe disease but a minority of patients show progressive and recurrent respiratory infections with obstructive lung disease. IgG3 deficiency may be seen in association with IgG1 deficiency. Levels are reduced in some patients with juvenile diabetes mellitus and in the Wiskott Aldrich syndrome.

IgG4 deficiency as an isolated event is exceedingly rare.

Raised concentrations of IgG4 are seen in atopic dermatitis, asthma, some parasitic diseases and cystic fibrosis. The role of IgG4 in the pathogenesis of allergic disease is controversial but it is responsive to challenge by environmental antigens and is increased in patients undergoing hyposensitisation therapy.
The knowledge of IgG subclass concentrations will play an increasing role in understanding of the immune deficiency syndromes, the susceptibility to recurrent infection and of hypersensitivity states. The screening of children with recurrent infections for the IgG2 deficiency state would appear to be a rewarding exercise as these children benefit from replacement immunoglobulin therapy.
Normal values for total serum IgG and for the IgG subclasses may mask a functional deficiency of one or more subclasses in response to specific antigens. Functional antibody assays are available on consultation and may help to elucidate these complex clinical problems.
Whilst it is possible to subclass IgG myeloma proteins, this is of doubtful value save for the identification of the increased hyperviscosity risk associated with IgG3 myeloma .

Sample requirement: 2 mL serum.

Reference ranges:
5th-95th centile ranges for IgG subclasses – all values in g/L.in relation to SPS-01.

IgG1 IgG2 IgG3 IgG4
Cord Blood
3.6 – 8.4
1.2 – 4.0
0.3 -1.5
– 6 months
1.5 – 3.0
0.3 – 0.5
0.1 – 0.6
– 2 years
2.3 – 5.8
0.3 – 3.9
0.1 – 0.8
– 5 years
2.3 – 6.4
0.7 – 4.5
0.1 – 1.1
– 10 years
3.6 – 7.3
1.4 – 4.5
0.3 – 1.1
– 15 years
3.8 – 7.7
1.3 – 4.6
0.2 – 1.2
3.2 – 10.2
1.2 – 6.6
0.2 – 1.9

In adults IgG3 concentrations are higher in females than in males, and IgG4 higher in males than females. No sex difference is seen before the age of 15 years.

Centres offering this assay:
Cardiff UHW PRU Diagnostic Service
London St George’s Hospital PRU Diagnostic Service
Sheffield Northern General’s PRU Diagnostic Service

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