Diminished concentrations of IgG subclass proteins may occur in the context of hypogammaglobulinemia (eg, in common variable immunodeficiency where all immunoglobulin classes are generally affected) or deficiencies may be selective, usually involving IgG2.

Deficiency of IgG1 usually occurs in patients with severe immunoglobulin deficiency involving other IgG subclasses.

Deficiency of IgG2 is more heterogeneous and can occur as an isolated deficiency or in combination with deficiency of immunoglobulin A (IgA), or of IgA and other IgG subclasses. Most patients with IgG2 deficiency present with recurrent infections, usually sinusitis, otitis, or pulmonary infections. Children with deficiency of IgG2 often have deficient antibody responses to polysaccharide antigens including bacterial antigens associated with Haemophilus influenzae type B and Streptococcus pneumoniae. Isolated deficiencies of IgG3 or IgG4 occur rarely, and the clinical significance of these findings is not clear.

May mean a long-term (chronic) infection, such as AIDS, is present. Levels of IgG are higher in IgG MGUS, IgG multiple myeloma, long-term hepatitis, and multiple sclerosis (MS). In multiple myeloma, tumor cells make only one type of IgG antibody (monoclonal); the other conditions cause an increase in many types of IgG antibodies (polyclonal).