Protein Electrophoresis, Serum

A principal use of this test is in the detection of monoclonal gammopathies. These are usually found in association with hemic neoplasms, especially multiple myeloma. They also occur in other benign and malignant conditions. Any such protein detected should be identified by an alternative technique, such as immunofixation or immunoelectrophoresis.

Other applications of serum protein electrophoresis include the following:

• Serum protein evaluation, nutritional status.

• Work-up for liver disease, including cirrhosis and chronic active hepatitis. In liver disease, albumin is apt to be decreased. A₂ may be low. γ is often polyclonal (ie, dome-shaped) in many cases of cirrhosis. The normal depression between β and γ area may be missing in hepatic cirrhosis; this is called beta-gamma bridging. Polyclonal gammopathy occurs in a wide range of entities which have in common chronic immunologic stimulation (eg, sarcoidosis).

• The γ-globulin may present an isolated increase. The γ-globulin fraction includes IgG, IgA, IgM, IgD, and IgE. Diffuse polyclonal elevation indicates a chronic immunologic process such as that found with liver disease (eg, chronic active hepatitis, cirrhosis), collagen diseases (eg, systemic LE, rheumatoid arthritis), neoplasms (eg, some instances of Hodgkin disease), and chronic myelomonocytic leukemia. Several small bands (oligoclonal) are seen in patients with hepatitis, immune complex diseases, acquired immunodeficiency syndrome, and angioimmunoblastic lymphoadenopathy.

• Monoclonal gammopathy (M protein) patterns may be benign, especially when small and not increasing, but monoclonal gammopathies relate especially to myeloma, primary amyloidosis, macroglobulinemia of Waldenström, and occasional malignant lymphomas. These are tall, narrow, spire-shaped formations as seen in densitometer tracings. Although small monoclonal gammopathies may be found with benign diseases, they may also be detected with early or evolving plasma cell dyscrasias or malignant lymphoproliferative diseases. Therefore, such small monoclonal gammopathies are regarded as “monoclonal gammopathies of undetermined significance.” All patients with monoclonal gammopathies should be followed with periodic serum protein electrophoresis to differentiate stable from increasing M spikes. Increasing M proteins require further evaluation (bone marrow examination, skeletal x-ray studies, urinary protein electrophoresis, immunoelectrophoretic or immunofixation studies, and so forth).

• Low γ-globulin: Although gamma globulins may decrease slightly with advancing age, any decrease below the normal range if unexplained by obvious causes of protein loss (such as known renal disease), should be further evaluated with a urine immunofixation to detect possible monoclonal free light chains (Bence Jones protein) in the urine. Hypogammaglobulinemia is also seen in many patients with B-cell lymphoproliferative disorders such as chronic lymphocytic leukemia. They may be decreased with cytotoxic or immunosuppressive drug therapy (long-term steroid use, antineoplastic chemotherapy), malignant lymphoproliferative diseases, and plasma cell dyscrasias (multiple myeloma), and adult common variable immunodeficiency syndrome. If there is clinical history of susceptibility to infection in the patient or the family, then quantitative immunodiffusion or nephelometric assay for IgG, IgA, and IgM may prove helpful. Attention to lymphocytes in the peripheral blood film, presence or absence of hepatosplenomegaly and in patients over age 40, presence or absence of light chains in urine immunoelectrophoresis or immunofixation may be relevant (eg, light chain disease).

• High α₂: A₂ includes inflammation-reactive fractions, and may be increased with neoplasms (eg, renal cell carcinomas), acute infections, rheumatic fever, arteritis, nephrotic syndromes, and other inflammatory states. A₂-macroglobulin is increased in pregnancy and with diabetes mellitus. Healthy children may have higher levels of α₂-macroglobulin than adults.

• Low α₂: One of the important fractions of α₂ is haptoglobin. Depression of haptoglobin may indicate hemolysis. A₂-globulins may be decreased in hepatocellular damage. Trauma and transfusions may cause a drop in α₂.

• A₁ globulins are increased in active inflammatory or neoplastic diseases.

• Low α₁ or flat α₁ curve: α₁-antitrypsin is responsible for 90% of serine antiprotease activity in serum. Its deficiency is due to a genetic abnormality that must be investigated because it leads to emphysema and cirrhosis. If the patient has emphysema, a family history of emphysema, or liver disease of uncertain type, α₁-antitrypsin assay and phenotype may be indicated.

• Albumin is better measured by electrophoresis than by chemical methods when is is relevant to do so. Electrophoresis permits diagnosis of rare entities such as analbuminemia and bisalbuminemia. Albumin is increased in dehydration and decreased in a wide variety of subacute, subchronic, and chronic diseases including liver, renal, and gastrointestinal diseases, malnutrition, and cachexia.

• Decreased total protein with essentially normal pattern might indicate dietary deficiency or hemodilution (IV fluid running at time of venipuncture?)

• Significantly elevated total protein with essentially normal pattern is likely to be secondary to dehydration.

• Significantly low total protein and albumin, increased α₂, and low γ is prototypical of the nephrotic syndrome.