What this test measures
Serum proteins are separated electrophoretically into 5 bands at alkaline pH: albumin, alpha-1, alpha-2, beta, and gamma. Gamma globulins contain immunoglobulins; abnormalities here reveal monoclonal gammopathies (a tall, sharp "M-spike" indicating clonal plasma cell expansion — MGUS, smouldering myeloma, multiple myeloma, Waldenström's macroglobulinaemia, light-chain disease, primary amyloidosis). Polyclonal hypergammaglobulinaemia (broad gamma elevation) suggests chronic infection, autoimmune disease, or chronic liver disease.
Why it matters
Indian myeloma practice routinely uses SPEP as part of the diagnostic workup — alongside serum free light chains (FLC) and serum immunofixation (IFE). Bone pain in an older adult, unexplained anaemia, raised total protein, hypercalcaemia, renal failure, or recurrent infections are all triggers for SPEP. UPEP detects light-chain disease (Bence-Jones protein) that may be invisible on serum protein. Reflex to IFE for confirmation of M-band type (IgG kappa most common, then IgA kappa, IgG lambda, IgA lambda).
How to prepare
No fasting required. For SPEP: serum sample. For UPEP: 24-hour urine (best) or concentrated random urine. Disclose any current infection / inflammation (raises alpha bands), IV immunoglobulin (mimics gammopathy), recent vaccinations, and current immunosuppressants.
Markers & reference ranges
Reference ranges below are typical adult values. Your lab's reported range may differ slightly based on the assay platform and patient demographics — always read your report against the range printed on it.
| Marker | Normal range | If low | If high |
|---|---|---|---|
| Albumin (%) | 55 – 65% | Low — liver disease, nephrotic syndrome, malnutrition, sepsis. | High — dehydration. |
| Gamma globulin (%)[1][2] | 11 – 21% | Hypogammaglobulinaemia — primary immunodeficiency, secondary (CLL, multiple myeloma paradoxically lowers normal Ig, drug-induced). | Polyclonal hypergammaglobulinaemia (broad-based) — chronic infection (HIV, TB), autoimmune disease (SLE, RA), chronic liver disease (cirrhosis, AIH). Monoclonal (M-spike, sharp narrow band) — MGUS, smouldering or active myeloma, Waldenström's, light-chain disease — reflex to immunofixation + free light chains. |
| Total Protein (g/dL) | 6.0 – 8.0 | Low — albumin loss (nephrotic syndrome, liver disease, malnutrition). | High — monoclonal gammopathy, chronic inflammation, dehydration. Reflex to SPEP if unexplained. |
SPEP patterns and clinical significance
| Pattern | Likely cause |
|---|---|
| Sharp narrow M-spike in gamma | MGUS / myeloma / Waldenström — confirm with IFE + FLC + BM biopsy |
| Polyclonal hypergamma (broad) | Chronic infection, autoimmune disease, cirrhosis |
| Hypogammaglobulinaemia | Immunodeficiency, CLL, light-chain myeloma |
| Low albumin + low gamma + raised alpha-2 | Nephrotic syndrome |
| Low albumin + raised gamma | Chronic liver disease |
| Beta-gamma bridging | Cirrhosis (IgA elevation) |
Frequently asked questions
I have an M-spike — do I have cancer?
Not necessarily. About 60% of patients with M-spike have MGUS (Monoclonal Gammopathy of Undetermined Significance) — benign, ~1% per year risk of progression to myeloma. The next step is full myeloma workup: serum FLC, IFE, urine UPEP, calcium, creatinine, Hb, skeletal survey or PET-CT, bone marrow biopsy.
What is the difference between SPEP and IFE?
SPEP screens for protein abnormalities (gives "M-spike"). IFE (Immunofixation Electrophoresis) identifies the heavy chain (IgG, IgA, IgM, IgD, IgE) and light chain (kappa, lambda) of the M-protein — used to confirm and characterise.
Should I also do urine UPEP?
Yes for myeloma workup — light-chain disease may produce a normal SPEP with monoclonal protein only in urine. 24-hour UPEP + serum/urine IFE + free light chains cover all light-chain myelomas.
Will infection affect the result?
Yes — acute infection raises acute-phase reactants (alpha-1, alpha-2), and chronic infection raises gamma (polyclonal). Repeat after infection resolves if the picture is unclear.
How often should MGUS be monitored?
Risk-stratified — low risk MGUS (IgG, M-spike < 1.5 g/dL, normal FLC ratio): re-test in 6 months, then annually. Higher risk: 3-6 monthly. Progression to myeloma is at ~1%/year on average.
Do I need a bone marrow biopsy?
For MGUS with low-risk features, no. For myeloma diagnosis (M-spike + symptoms or organ damage), yes — bone marrow with plasma cell percentage and FISH for cytogenetics is standard.
Related Histopathology / Cytology tests
Tests commonly ordered alongside PROTEIN ELECTROPHORESIS, or that help interpret an unexpected result.
Sources & references
- International Myeloma Working Group · accessed 2026-05-30T00:00:00.000Z
- NIH MedlinePlus — Protein Electrophoresis · accessed 2026-05-30T00:00:00.000Z
- Mayo Clinic Labs — Protein Electrophoresis · accessed 2026-05-30T00:00:00.000Z
- BSH — Myeloma Diagnostic Workup · accessed 2026-05-30T00:00:00.000Z
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