serum protein electrophoresis
Summary
Serum protein electrophoresis (SPEP) is a lab test that separates serum proteins by size and charge into albumin and globulin fractions (alpha-1, alpha-2, beta, gamma) to detect abnormal protein patterns. It is most commonly used to screen for monoclonal gammopathies such as multiple myeloma and to evaluate conditions causing hypoalbuminemia or polyclonal hypergammaglobulinemia.
Detail
SPEP works by applying an electrical current to a serum sample on a gel or capillary medium, causing proteins to migrate based on their charge and size, producing a characteristic banding pattern. The normal pattern shows a large albumin peak followed by smaller alpha-1, alpha-2, beta, and gamma globulin peaks.
Key clinical applications: - Monoclonal gammopathy (M-spike): A sharp, narrow spike in the gamma (or sometimes beta) region suggests a plasma cell dyscrasia such as multiple myeloma, Waldenström macroglobulinemia, MGUS, or amyloidosis. This should prompt follow-up with serum immunofixation electrophoresis (SIFE) to identify the specific immunoglobulin class and light chain type, plus serum free light chain assay and urine protein electrophoresis (UPEP) for Bence Jones proteins. - Polyclonal gammopathy: A broad-based increase in the gamma region reflects chronic inflammation, infection, autoimmune disease (e.g., SLE, rheumatoid arthritis), or chronic liver disease (cirrhosis often shows beta-gamma bridging due to increased IgA). - Hypoalbuminemia: Decreased albumin peak seen in nephrotic syndrome, liver disease, malnutrition, or chronic inflammatory states (negative acute phase reactant). - Alpha-1 antitrypsin deficiency: Decreased or absent alpha-1 band. - Acute phase reaction: Increased alpha-1 and alpha-2 globulins (haptoglobin, ceruloplasmin) with normal or low albumin.
Pathophysiologic correlation: In multiple myeloma, a clonal plasma cell population overproduces a single immunoglobulin (monoclonal protein/paraprotein), producing the characteristic M-spike. This is often accompanied by elevated total protein, anemia, renal insufficiency, hypercalcemia, and lytic bone lesions (CRAB criteria). MGUS shows a similar but smaller M-spike without end-organ damage and requires monitoring for progression to myeloma.
Clinical significance: SPEP is a key initial screening test whenever myeloma, amyloidosis, or a paraproteinemia is suspected, particularly in older patients presenting with unexplained anemia, renal failure, bone pain, or hypercalcemia. It is also useful in evaluating chronic liver disease, nephrotic syndrome, and chronic inflammatory conditions.
Sources
- First Aid for the USMLE Step 1
- Robbins and Cotran Pathologic Basis of Disease
- UpToDate: Serum protein electrophoresis
- Harrison's Principles of Internal Medicine
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