What is SPEP Testing?
Serum Protein Electrophoresis (SPEP) is a laboratory test that separates blood proteins based on their electrical charge and size to detect and quantify monoclonal proteins (M-proteins), primarily used to diagnose and monitor plasma cell disorders such as multiple myeloma, as well as evaluate polyneuropathies and other protein abnormalities. 1
Primary Clinical Applications
Detection of Monoclonal Gammopathies
- SPEP identifies the presence, type, and quantity of M-proteins (abnormal antibodies produced by clonal plasma cells), appearing as a characteristic monoclonal spike (M-spike) on the electrophoresis pattern, typically in the gamma region. 1
- The test is fundamental for diagnosing multiple myeloma, Waldenström's macroglobulinemia, monoclonal gammopathy of undetermined significance (MGUS), and related plasma cell disorders. 1, 2
- Monoclonal gammopathies are significantly more common in patients with polyneuropathy (10% prevalence) compared to the general population, making SPEP a high-yield screening test in this context. 3
Evaluation of Polyneuropathy
- SPEP is one of the three highest-yield screening tests for distal symmetric polyneuropathy (DSP), alongside blood glucose and serum B12 with metabolites. 3
- However, serum protein immunofixation electrophoresis (IFE) is more sensitive than SPEP, especially for detecting small or non-malignant monoclonal gammopathies—IFE identified 17% of monoclonal gammopathies that SPEP missed. 3
How the Test Works
Technical Methodology
- SPEP separates serum proteins into distinct fractions based on their physical properties: albumin, alpha-1 globulin, alpha-2 globulin, beta globulin, and gamma globulin. 2, 4
- The resulting pattern displays reasonably predictable changes in response to acute inflammation, malignancy, trauma, necrosis, infarction, burns, and chemical injury. 2
- A homogeneous spike-like peak in a focal region (usually gamma-globulin zone) indicates a monoclonal gammopathy requiring further investigation. 2
Interpretation and Follow-Up
Abnormal Findings
- When SPEP shows an M-spike or abnormal pattern, mandatory follow-up testing includes serum immunofixation electrophoresis (SIFE) to identify the exact immunoglobulin type (IgG, IgA, IgM) and light chain (kappa or lambda). 1
- Additional required tests include quantitative immunoglobulin levels, serum free light chain (FLC) assay with kappa/lambda ratio, and 24-hour urine collection for urine protein electrophoresis (UPEP) and urine immunofixation. 1
- The combination of SPEP plus serum free light chain analysis achieves 100% sensitivity for detecting plasma cell disorders. 1
Clinical Significance of M-Protein Levels
- MGUS typically shows M-protein less than 30 g/L, while multiple myeloma typically shows higher levels. 1
- The height and area under the M-spike can be quantified to track disease burden and monitor treatment response. 1
Important Limitations and Pitfalls
Sensitivity Concerns
- Approximately 15-20% of myeloma cases produce only light chains (not complete antibodies), which may not create a visible spike on standard SPEP and require urine testing or serum free light chain assays for detection. 1
- About 3% of patients have truly non-secretory myeloma with no detectable M-protein on either SPEP or UPEP, highlighting the importance of additional diagnostic tests. 1
- Serum immunofixation electrophoresis is more sensitive than SPEP and should be used when clinical suspicion is high despite negative SPEP. 3
Referral Indications
- Any detected monoclonal protein on SPEP should prompt referral to a hematologist/oncologist, with urgent referral (within 1-2 weeks) recommended for patients with significant M-protein spike, accompanying symptoms, anemia, renal dysfunction, or hypercalcemia. 1