Immunoglobulin G Subclasses

Approximately 75% of total serum immunoglobulin in adults is IgG. It can be further divided in four subclasses, named, in order of decreasing abundance IgG1, IgG2, IgG3, and IgG4. IgG1 and IgG2 comprise 85% of the total. IgG1 is similar to IgG3 and IgG2 resembles IgG4. IgG1 and IgG3 are the most effective at activating complement. 

The four subclasses differ in the constant regions of their heavy chains. Although their amino acid sequence is 90% identical, each subclass is unique with respect to antigen binding, immune complex formation, complement activation, triggering of effector cells, half-life, and placental transport.

A patient may have a normal total IgG concentration yet still have a significant decrease in one subclass. IgG1 deficiencies are associated with EBV infections. IgG2 deficiencies predispose to sinorespiratory infections and infections with encapsulated bacteria.  IgG3 deficiencies are associated with sinusitis and otitis media. IgG4 deficiencies are rare but are associated with allergies, ataxia telangiectasia, and sinorespiratory infections. IgG4 levels are elevated in IgG4-related diseases. 

IgG subclasses are measured by enzyme-linked immunosorbent assays, nephelometry, and turbidimetry. The diagnosis of  an IgG subclass deficiency requires one or more subclasses to be decreased in the presence of normal concentrations of IgG, IgA, and IgM.

Adult reference ranges are:

Specimen requirement is one plain red top or SST tube of blood.

References

Heiner DC, Significance of immunoglobulin G subclasses, Amer J Med.1984;76(3):1-6. 

Vidarsson G, Dekkers G, Rispens T. IgG subclasses and allotypes: from structure to effector functions. Front Immunol. 2014 Oct 20;5:520.

Antony R Parker, et al, The Clinical Utility of Measuring IgG Subclass Immunoglobulins During Immunological Investigation for Suspected Primary Antibody Deficiencies, Laboratory Medicine, 2017;48(4):314–325.