What is SPEP/UPEP?
SPEP (Serum Protein Electrophoresis) and UPEP (Urine Protein Electrophoresis) are laboratory tests that separate and measure different proteins in blood and urine to detect and quantify monoclonal proteins (M-proteins), which are abnormal antibodies produced by clonal plasma cells in disorders like multiple myeloma. 1
How These Tests Work
SPEP separates serum proteins based on their physical properties and electrical charge, creating distinct bands representing different protein fractions (albumin, alpha-1, alpha-2, beta, and gamma globulins). 2 When a monoclonal protein is present, it appears as a sharp, homogeneous spike (M-spike) typically in the gamma region, though it can appear in the beta region. 1, 3
UPEP performs the same separation technique on a 24-hour urine collection to detect M-proteins that are excreted in urine, particularly light chains (Bence Jones proteins). 4
Primary Clinical Applications
These tests serve four main purposes in plasma cell disorder evaluation:
- Initial screening for suspected multiple myeloma, Waldenström's macroglobulinemia, monoclonal gammopathy of undetermined significance (MGUS), and related conditions 1
- Quantifying M-protein levels to establish baseline disease burden 4
- Monitoring treatment response by tracking changes in M-protein concentration over time 4
- Detecting disease recurrence during surveillance 1
Diagnostic Workflow After Abnormal Results
When SPEP shows an M-spike, the National Comprehensive Cancer Network mandates specific follow-up testing: 1
- Serum immunofixation electrophoresis (SIFE) to identify the exact immunoglobulin type (IgG, IgA, IgM) and light chain (kappa or lambda) 4, 1
- Quantitative immunoglobulin levels (IgG, IgA, IgM) to assess immune paresis 1
- Serum free light chain (FLC) assay with kappa/lambda ratio 4, 1
- 24-hour urine collection for total protein, UPEP, and urine immunofixation electrophoresis (UIFE) 4, 1
Critical Limitations and Pitfalls
SPEP has significant sensitivity limitations. In patients with lytic bone lesions, SPEP demonstrates only 71% sensitivity and 47% positive predictive value for plasma cell neoplasms, though it maintains 94% negative predictive value. 5 This means a negative SPEP does not rule out myeloma.
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 An additional 3% of patients have truly non-secretory myeloma with no detectable M-protein on either SPEP or UPEP. 4
The combination of SPEP plus serum free light chain analysis achieves 100% sensitivity for detecting plasma cell disorders, superior to SPEP plus UPEP. 6 This modern approach can eliminate the need for 24-hour urine collection in initial screening, though UPEP remains necessary for monitoring patients with measurable urinary M-proteins. 4
Interpretation Nuances
Renal impairment causes false-positive elevations in serum free light chain ratios up to 3.1 (normal 0.26-1.65) without true plasma cell disorder, requiring interpretation in context of serum creatinine levels. 7
Polyclonal gammopathies (broad-based elevation in gamma region without sharp spike) indicate reactive or inflammatory processes, not clonal plasma cell disorders, and must be distinguished from monoclonal patterns. 2
When to Refer
Any detected monoclonal protein on SPEP requires hematology/oncology referral. 1 Urgent referral within 1-2 weeks is mandatory for patients with significant M-protein spike accompanied by anemia, renal dysfunction, hypercalcemia, or bone lesions. 1