What does Serum Protein Electrophoresis (SPEP) test for?

Serum Protein Electrophoresis (SPEP) Test: Detection of Monoclonal Proteins

Serum protein electrophoresis (SPEP) primarily tests for the presence of monoclonal proteins (M-proteins) in the blood, which are abnormal antibodies produced by clonal plasma cells, most commonly associated with multiple myeloma and related plasma cell disorders. 1

What SPEP Detects

SPEP separates serum proteins based on their physical properties, specifically their electrical charge and size, allowing identification of:

• Monoclonal gammopathies: Characterized by a spike-like peak in the gamma-globulin region

  • Multiple myeloma
  • Waldenstrom's macroglobulinemia
  • Solitary plasmacytoma
  • Smoldering multiple myeloma
  • Monoclonal gammopathy of undetermined significance (MGUS)
  • Amyloidosis
  • Heavy chain disease

• Polyclonal gammopathies: Broader elevation in the gamma region caused by:

  • Inflammatory conditions
  • Infections
  • Liver disease
  • Autoimmune disorders

Clinical Utility

SPEP is particularly valuable for:

1. Screening for plasma cell disorders - Detects the M-protein component in serum 1
2. Quantifying the M-protein - Helps track disease progression and treatment response 1
3. Identifying protein pattern abnormalities - Changes in albumin or globulin fractions can indicate various disorders 2

Limitations of SPEP

• Limited sensitivity - SPEP has a sensitivity of only about 71% for detecting plasma cell neoplasms 3
• False negatives - Approximately 3% of multiple myeloma patients have nonsecretory disease with no detectable M-proteins on SPEP 1, 4
• Poor positive predictive value - Only 47% for plasma cell neoplasms when used alone 3

Complementary Tests

Due to SPEP's limitations, additional tests are recommended:

• Serum immunofixation electrophoresis (SIFE) - More sensitive for detecting small monoclonal proteins 4
• Serum free light chain (FLC) assay - Detects free kappa and lambda light chains, especially valuable for:
  • Nonsecretory myeloma
  • Light chain amyloidosis
  • Oligosecretory myeloma 1
• Urine protein electrophoresis (UPEP) and urine immunofixation electrophoresis (UIFE) - Detect monoclonal proteins excreted in urine 1
• Quantitative immunoglobulin levels (IgG, IgA, IgM) - Provide information about specific antibody types 1

Clinical Algorithm for SPEP Interpretation

1. Normal pattern: No further testing needed unless clinical suspicion remains high
2. Monoclonal spike detected:
   • Quantify the M-protein
   • Perform SIFE to characterize the protein
   • Order serum FLC assay
   • Collect 24-hour urine for UPEP and UIFE
   • Consider bone marrow biopsy and skeletal survey to evaluate for multiple myeloma
3. Polyclonal increase in gamma region:
   • Evaluate for underlying inflammatory or infectious conditions
4. Hypogammaglobulinemia (decreased gamma region):
   • Consider immunodeficiency disorders or protein-losing conditions

Important Pitfalls to Avoid

• Relying solely on SPEP - The high negative predictive value (94%) makes it useful for ruling out disease, but its limited sensitivity means it should not be used alone 3
• Failing to perform urine studies - Some patients excrete monoclonal proteins only in urine 1
• Not using consistent testing methods - Once an M-protein is quantified, the same test must be used for serial monitoring to ensure accurate relative quantification 1
• Overlooking nonsecretory disease - Consider serum FLC assay in patients with suspected plasma cell disorders but negative SPEP 4

SPEP remains a valuable and relatively inexpensive screening tool for plasma cell disorders, but its limitations must be recognized, and complementary testing should be performed when clinically indicated.