hyperglobulinemia

Hyperglobulinemia is a condition in which the concentration of globulins in the blood is elevated. Globulins are a group of plasma proteins that includes immunoglobulins (antibodies) and various transport and inflammatory proteins. Clinically, hyperglobulinemia is often identified by an increased globulin fraction (total protein minus albumin) or by a rise in the gamma region on serum protein electrophoresis. The raised globulins may be polyclonal or monoclonal.

Polyclonal hyperglobulinemia reflects widespread immune activation and is typically seen with chronic inflammation or infection, autoimmune diseases, and often liver disease. Monoclonal hyperglobulinemia results from clonal proliferation of plasma cells or lymphoplasmacytic cells and includes conditions such as multiple myeloma, Waldenström macroglobulinemia, monoclonal gammopathy of undetermined significance (MGUS), and plasmacytoma.

Diagnosis usually begins with basic chemistry to determine total protein, albumin, and globulin levels, followed by serum protein electrophoresis (SPEP) to identify monoclonal bands. If a monoclonal protein is detected, immunofixation helps classify the protein type (IgG, IgA, IgM, etc.). Quantitative immunoglobulin measurements (IgG, IgA, IgM) and assessment for underlying causes (liver function, infections, autoimmune markers) are often performed. Additional tests may include CBC, serum viscosity measurements, and imaging or bone marrow studies as indicated.

Management is directed at the underlying cause and the level of suspicion for a malignant clone. Mild, asymptomatic polyclonal hyperglobulinemia may require monitoring. Monoclonal gammopathies with clinically significant disease may require therapies such as plasmapheresis for hyperviscosity, chemotherapy, targeted agents, or antiviral treatment, depending on the specific diagnosis and disease activity.