What does protein electrophoresis of the serum test for?

What Serum Protein Electrophoresis Tests For

Serum protein electrophoresis (SPEP) is a quantitative screening test that separates and measures serum proteins—specifically albumin and globulin fractions (alpha-1, alpha-2, beta-1, beta-2, and gamma zones)—to detect monoclonal proteins (M-proteins) that indicate plasma cell disorders like multiple myeloma, as well as patterns of acute/chronic inflammation, liver disease, kidney disease, and immunodeficiencies. 1

Primary Clinical Purpose: Detection of Monoclonal Gammopathies

SPEP is fundamentally used to screen for and monitor monoclonal proteins associated with plasma cell proliferative disorders. 1 The test identifies:

• Monoclonal proteins (M-proteins): Abnormal immunoglobulins produced by clonal plasma cells that appear as a homogeneous spike-like peak in the gamma-globulin zone 2
• Multiple myeloma and related disorders: Including Waldenström's macroglobulinemia, monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma, light chain amyloidosis, and solitary plasmacytoma 1, 2

The NCCN guidelines explicitly state that SPEP, combined with serum immunofixation electrophoresis and serum free light chain assay, provides high sensitivity for screening plasma cell disorders and is essential for initial diagnostic workup. 1

What Each Protein Zone Reveals

Albumin Zone (Normal: 3.5-5.0 g/dL)

• Decreased albumin (hypoalbuminemia): Indicates liver disease, nephrotic syndrome, malnutrition, or protein-losing enteropathy 3, 2
• Your result of 4.8 g/dL is normal 1

Alpha-1 Zone (Normal: 0.1-0.4 g/dL)

• Decreased levels: Suggest alpha-1-antitrypsin deficiency, a hereditary protein disorder 2
• Increased levels: Indicate acute inflammation 3, 2
• Your result of 0.1 g/dL is at the lower normal limit 1

Alpha-2 Zone (Normal: 0.5-0.9 g/dL)

• Increased levels: Reflect acute or chronic inflammatory responses 3, 2
• Your result of 0.7 g/dL is normal 1

Beta Zones (Beta-1 and Beta-2, each Normal: 0.2-0.6 g/dL)

• Abnormal patterns: Can indicate iron deficiency anemia, transferrin abnormalities, or certain malignancies 2
• Your results (0.4 and 0.2 g/dL) are normal 1

Gamma Zone (Normal: 0.7-1.6 g/dL)

• Monoclonal spike: A sharp, narrow peak indicates monoclonal gammopathy requiring further workup with immunofixation 1, 2
• Polyclonal elevation: A broad-based increase suggests reactive/inflammatory processes, chronic infections, autoimmune diseases, or liver disease 2
• Hypogammaglobulinemia: Decreased levels indicate immunodeficiency 3
• Your result of 0.7 g/dL is at the lower normal limit 1

Clinical Applications Beyond Myeloma

SPEP serves as a diagnostic tool for multiple conditions:

• Inflammatory diseases: Acute and chronic inflammation produce predictable protein pattern changes 3, 2
• Liver disease: Shows characteristic albumin decreases and globulin increases 4, 2
• Renal disease: The International Kidney and Monoclonal Gammopathy Research Group emphasizes SPEP's role in detecting monoclonal gammopathy of renal significance (MGRS) 1
• Immunodeficiency disorders: Identifies agammaglobulinemia and hypogammaglobulinemia 3

Important Limitations and Follow-Up Testing

SPEP is a screening test—not diagnostic by itself. 1 Key caveats include:

• Immunofixation is more sensitive: When SPEP shows a monoclonal spike or clinical suspicion remains high despite normal SPEP, serum immunofixation electrophoresis must be performed to identify and type the specific monoclonal immunoglobulin 1
• Serum free light chain assay is essential: This test detects unbound light chains and is particularly valuable for light chain-only diseases and oligosecretory myeloma where SPEP may be negative 1
• 24-hour urine studies required: Urine protein electrophoresis and immunofixation detect urinary M-proteins in approximately 20% of myeloma patients 1

Interpretation of Your Results

Your SPEP shows no specific abnormalities—all protein fractions fall within normal ranges with no monoclonal spike detected. 1 This effectively rules out significant monoclonal gammopathy at this time. However:

• Your gamma zone (0.7 g/dL) and alpha-1 zone (0.1 g/dL) are at the lower limits of normal, which is not pathological but worth noting 1
• If clinical suspicion for plasma cell disorder exists despite normal SPEP, proceed with serum immunofixation and free light chain assay, as these are more sensitive 1