How do you interpret Serum Protein Electrophoresis (SPEP) lab results?

Interpreting Serum Protein Electrophoresis (SPEP) Results

SPEP interpretation requires systematic analysis of protein fractions, with particular attention to the gamma region for monoclonal proteins that may indicate plasma cell disorders such as multiple myeloma.

Normal SPEP Pattern and Components

SPEP separates serum proteins into five main fractions based on their physical properties:

1. Albumin - Largest peak, typically 50-60% of total protein
2. Alpha-1 - Small peak, 2-5% of total protein
3. Alpha-2 - Moderate peak, 7-13% of total protein
4. Beta - Moderate peak, often with two components (beta-1 and beta-2), 8-14% of total protein
5. Gamma - Broad region, 10-20% of total protein

Abnormal Patterns and Their Interpretation

Monoclonal Gammopathies

• Key Finding: Sharp, narrow "spike" or "M-spike" in gamma region (occasionally beta region)

• Interpretation: Indicates monoclonal protein production, suggestive of:

  • Multiple myeloma
  • Monoclonal gammopathy of undetermined significance (MGUS)
  • Waldenstrom's macroglobulinemia
  • Solitary plasmacytoma
  • Amyloidosis 1, 2

• Quantification: M-protein is measured in g/dL or g/L using perpendicular drop or tangent skimming methods 3

Polyclonal Gammopathies

• Key Finding: Broad-based elevation in gamma region
• Interpretation: Indicates reactive or inflammatory process, not malignant 2, 4
• Common causes: Chronic infection, liver disease, autoimmune disorders

Hypogammaglobulinemia

• Key Finding: Decreased gamma region
• Interpretation: Consider immunodeficiency disorders or protein-losing conditions 2

Other Abnormalities

• Beta-gamma bridging: Seen in liver disease or inflammatory conditions
• Decreased albumin: Malnutrition, liver disease, protein-losing enteropathy, nephrotic syndrome
• Increased alpha-2: Acute phase reactant elevation in inflammation

Comprehensive Diagnostic Approach

When interpreting SPEP, follow this algorithm:

1. Assess overall pattern:

   • Normal pattern → No further testing unless clinical suspicion remains high
   • Abnormal pattern → Proceed to next steps

2. If monoclonal spike detected:

   • Quantify M-protein
   • Order serum immunofixation electrophoresis (SIFE) to identify type
   • Order serum free light chain (FLC) assay
   • Order 24-hour urine for protein electrophoresis (UPEP) and immunofixation (UIFE) 1, 2

3. If polyclonal increase in gamma region:

   • Evaluate for underlying inflammatory or infectious conditions

4. If hypogammaglobulinemia:

   • Consider immunodeficiency disorders or protein-losing conditions

Important Considerations

• Quantitative immunoglobulin levels (IgG, IgA, IgM) provide additional information about specific antibody types 1

• Serum free light chain assay is essential as part of initial workup, especially when SPEP is negative but clinical suspicion for plasma cell disorder remains high 1

• Consistent methodology is crucial for serial monitoring - always use the same testing method for accurate relative quantification 1

• Location of M-protein peak should be documented as it serves as a "delta check" for subsequent samples 5

• Fibrinogen interference can mimic a monoclonal spike - a γ/IgG ratio >1.13 suggests fibrinogen rather than true monoclonal protein 6

Common Pitfalls to Avoid

• Overlooking nonsecretory disease: Approximately 3% of multiple myeloma patients have no detectable M-proteins on SPEP 1

• Missing small M-proteins: Lower concentrations of M-proteins have greater imprecision and decreased accuracy 3

• Failing to perform urine studies: Some patients may have light chain disease with minimal or no serum M-protein 1, 2

• Misinterpreting therapeutic monoclonal antibodies: Treatments like daratumumab or elotuzumab can appear as monoclonal proteins on SPEP 3

• Relying solely on SPEP: The sensitivity of SPEP alone for detecting monoclonal proteins is approximately 71%, highlighting the need for complementary testing 2

By systematically analyzing the SPEP pattern and following up with appropriate additional testing, clinicians can accurately identify and monitor patients with plasma cell disorders and other protein abnormalities.