Serum Protein Electrophoresis: Reference Range, Interpretation, Collection and Panels

Various disease states or conditions alter the pattern of proteins in electrophoresis (see Table 1 below).

Table 1. Serum Protein Fractions and Conditions Associated with an Increased or Decreased Level (Open Table in a new window)

Serum Protein Fraction

Increased

Decreased

Albumin

Severe dehydration

Malnutrition, cachexia, liver disease, nephrotic syndrome, protein-losing enteropathies, severe burns

Alpha-1

Inflammatory states, pregnancy

Alpha-1 antitrypsin deficiency

Alpha-2

Inflammatory states, nephrotic syndrome, oral contraceptive use, steroid use, hyperthyroidism

Hemolysis, liver disease

Beta

Hyperlipidemia, iron-deficiency anemia

Hypo-B-lipoproteinemia, malnutrition

Gamma

Polyclonal and Monoclonal Gammopathies

Agammaglobulinemia, hypogammaglobulinemia

Monoclonal gammopathy

A dense narrow band that is composed of a single class of immunoglobulins secreted by an abnormally expanded clone of plasma cells is known as M-protein (paraprotein, monoclonal protein, or M-component).
[3, 4] An M-protein usually presents as a single narrow peak, resembling a “church spire,” in the gamma, beta, or alpha-2 region of the densitometer tracing, or as a dense, discrete band on the agarose gel (see image below).

Monoclonal pattern serum protein electrophoresis (SPEP).

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The monoclonal antibody must be present at a concentration of at least 0.5 g/dL in order to be accurately identified using SPEP. This corresponds to approximately 109 antibody-producing cells.
[5] Plasma cell disorders are typically associated with the presence of an M-protein (see Table 2 below). In addition, an M component may be detected in other lymphoid malignancies like chronic lymphocytic leukemia, any B- or T- cell lymphomas, breast cancer, colon cancer, cirrhosis, sarcoidosis, and other autoimmune disorders.

Conditions associated with a monoclonal increase in the gamma region are as follows:

• Multiple myeloma

• Smoldering myeloma

• Monoclonal gammopathy of undetermined significance (MGUS)

• Waldenstrom macroglobulinemia

• Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS syndrome)

• Solitary plasmacytoma

• Castleman disease

• AL amyloidosis

• Heavy chain deposition disease

• Light chain deposition disease

Polyclonal gammopathy

Infectious, Inflammatory or various reactive processes may be associated with a broad-based peak or band in the gamma region (Figure 4). This pattern suggests a polyclonal increase in immunoglobulins. Liver disease, autoimmune disease, chronic viral or bacterial infections and various malignancies may cause a polyclonal rise in the gamma fraction (see Table 2 below).

Polyclonal pattern serum protein electrophoresis (SPEP).

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Table 2. Diseases Associated with a Polyclonal Gammopathy (Open Table in a new window)

Condition

Examples

Liver disease

Cirrhosis, autoimmune or viral hepatitis

Connective tissue diseases

Rheumatoid arthritis, systemic lupus erythematosus, scleroderma, Sjogren syndrome

Infection

Bacterial: osteomyelitis, endocarditis, osteomyelitis

Viral: HIV/AIDS, hepatitis C, Epstein-Barr virus

Hematologic disorders/malignancies

Non-Hodgkin lymphoma, chronic lymphocytic leukemia, thalassemia, sickle cell anemia

Nonhematologic malignancies

Lung, ovarian, gastric malignancies, hepatocellular carcinoma

Considerations

The presence of an M-protein may be missed if the level is too small to be detected using SPEP. In cases where a high suspicion for a clonal plasma cell disorder is high, more sensitive tests such as a serum immunofixation or free light chain assay should be performed. In addition, when either alpha-1 antitrypsin deficiency or immunoglobulin deficiency, specific quantitation is indicated as SPEP is insensitive in these cases.

Therapeutic monoclonal antibodies can interfere with results on SPEP and immunofixation. For example, a study by Scholl et al found that when casirivimab plus imdevimab, used in the treatment of coronavirus disease 2019 (COVID-19), was tested in serum samples, imdevimab produced “sustained assay interference (for at least 6 weeks) that could be misinterpreted as an IgG lambda monoclonal gammopathy.”
[6]