Clinical Information

The most abundant immunoglobulin isotype in human serum is IgG. IgG immunoglobulins are comprised of 4 subclasses designated IgG1 through IgG4. Of total IgG, approximately 65% is IgG1, 25% is IgG2, 6% is IgG3, and 4% is IgG4. Each IgG subclass contains structurally unique portions of the constant region of the gamma heavy chain.

The half-life of IgG1, IgG2, and IgG4 is around 22 days, while IgG3 has a half-life of approximately 7 days. The complement classical pathway is activated most strongly by IgG1 and IgG3 followed by weak strength in activation by IgG2. IgG4 does not activate complement. Clustering of multiple IgG molecules is required to activate complement. Both IgG1 and IgG3 bind Fc receptors on phagocytic cells, activate killer monocytes, and cross the placenta via receptor-mediated active transport. IgG1 is the principal IgG to cross the placenta, and neonatal concentrations are similar to maternal concentrations. Neonates have low production of IgG as the result of immaturity of their immune systems, and IgG concentrations fall through infancy, as the maternally-acquired antibody repertoire is cleared.

Measurement of the concentrations of IgG subclass proteins in serum is useful in evaluating patients with clinical signs and symptoms of humoral immunodeficiency or combined immunodeficiency (cellular and humoral). Diminished concentrations of one or more IgG subclass protein may occur in the context of hypogammaglobulinemia, eg, common variable immunodeficiency or deficiencies may be selective, usually involving IgG subclass 2. Deficiency of IgG subclass 1 usually occurs in patients with severe immunoglobulin deficiency involving other IgG subclasses. Deficiency of IgG subclass 2 is more heterogeneous and can occur as an isolated deficiency or in combination with deficiency of IgA or IgA and other IgG subclasses. Most patients with IgG2 deficiency present with recurrent infections, usually sinusitis, otitis, or pulmonary infections. Children with deficiency of IgG subclass 2 often have deficient antibody responses to polysaccharide antigens, including bacterial antigens associated with Haemophilus influenzae type B and Streptococcus pneumoniae. Isolated deficiencies of IgG subclass 3 or 4 occur rarely, and the clinical significance of these findings is not clear.