Understanding Serum Protein Electrophoresis (SPEP) Test
Serum Protein Electrophoresis (SPEP) is a critical diagnostic test that detects and evaluates monoclonal proteins (M-proteins) in the blood, primarily used to diagnose and monitor plasma cell disorders such as multiple myeloma and related conditions. 1
What SPEP Measures and Reveals
- SPEP separates serum proteins based on their physical properties, creating a pattern that helps identify abnormal protein distributions, particularly in the gamma globulin region where monoclonal proteins typically appear 2
- The test specifically identifies the presence, type, and quantity of M-proteins (monoclonal proteins), which are abnormal antibodies produced by clonal proliferation of plasma cells 1
- A spike-like peak in the gamma globulin zone indicates a monoclonal gammopathy, which may suggest multiple myeloma or other plasma cell disorders 2
- SPEP can also detect abnormal protein patterns in the beta region, which may represent certain types of monoclonal proteins 3
Clinical Significance and Interpretation
- SPEP is a fundamental component of the diagnostic workup for suspected plasma cell disorders, with results guiding further testing and management 1
- A normal SPEP shows a balanced distribution of proteins across different fractions (albumin, alpha-1, alpha-2, beta, and gamma globulins) 2
- Abnormal findings include:
- Monoclonal spike (M-spike): Indicates potential multiple myeloma, Waldenström's macroglobulinemia, or monoclonal gammopathy of undetermined significance (MGUS) 1, 2
- Polyclonal increase in gamma region: Suggests inflammatory or reactive processes rather than a malignancy 2
- Decreased albumin with increased gamma globulins: May indicate chronic inflammation or liver disease 2
Limitations and Additional Testing Needed
- SPEP alone has limited sensitivity (71%) and positive predictive value (47%) for diagnosing plasma cell disorders, requiring additional confirmatory tests 4
- When SPEP shows an abnormal pattern, follow-up testing should include 1, 5:
- Serum immunofixation electrophoresis (SIFE) to identify the specific type of abnormal antibody
- Quantitative immunoglobulin levels (IgG, IgA, IgM)
- Serum free light chain (FLC) assay
- 24-hour urine collection for total protein, urine protein electrophoresis (UPEP), and urine immunofixation electrophoresis (UIFE)
Clinical Applications
- SPEP is used for 1:
- Initial screening for plasma cell disorders
- Quantifying M-protein levels to track disease progression
- Monitoring response to treatment
- Detecting disease recurrence
- The same test method should be used for serial measurements to ensure accurate relative quantification 1
- Approximately 3% of multiple myeloma cases are non-secretory, showing no M-protein on SPEP or urine studies, requiring other diagnostic approaches 1
When to Refer to a Specialist
- Any detected monoclonal protein on SPEP should prompt referral to a hematologist/oncologist 5
- Urgent referral (within 1-2 weeks) is recommended for patients with significant M-protein spike, accompanying symptoms, anemia, renal dysfunction, or hypercalcemia 5
- The high negative predictive value (94%) of SPEP makes it useful for ruling out plasma cell disorders, but its limitations in sensitivity mean that clinical suspicion should guide further testing 4