The gamma globulin band as seen in conventional serum protein electrophoresis consists of 5 immunoglobulins. In normal serum, about 80% is immunoglobulin G (IgG), 15% is immunoglobulin A (IgA), 5% is immunoglobulin M (IgM), 0.2% is immunoglobulin D (IgD), and a trace is immunoglobulin E (IgE). Elevations of IgG, IgA, and IgM may be due to polyclonal immunoglobulin production. Monoclonal gammopathies of all types may lead to a spike in the gamma globulin zone seen on serum protein electrophoresis. Monoclonal elevations of IgG, IgA, IgD, and IgE characterize multiple myeloma. Monoclonal elevations of IgM occur in macroglobulinemia. Decreased immunoglobulin levels are found in patients with congenital deficiencies.

Increased serum immunoglobulin concentrations occur due to polyclonal or oligoclonal immunoglobulin proliferation in hepatic disease (hepatitis, liver cirrhosis), connective tissue diseases, acute and chronic infections, as well as in the cord blood of neonates with intrauterine and perinatal infections. Elevations of immunoglobulin G (IgG), immunoglobulin A (IgA), or immunoglobulin M (IgM) may occur in monoclonal gammopathies such as multiple myeloma (IgG, IgA), macroglobulinemia (IgM), primary systemic amyloidosis, monoclonal gammopathy of undetermined significance, and related disorders. Decreased levels are found in patients with primary or secondary immune deficiencies.