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Blood Test Tracker

SPEP Interpretation (Serum Protein Electrophoresis)

A written summary of your serum protein electrophoresis pattern: for example a normal pattern, a monoclonal spike, or a broad rise or fall in one protein group.

AI-verified against cited sources. Awaiting expert reviewAlso called SPEP, SPE, PEPLOINC 12851-2

What it is

Serum protein electrophoresis (SPEP) uses an electric current to sort the proteins in your blood into groups: albumin first, then alpha-1, alpha-2, beta and gamma globulins. A lab scientist or pathologist studies the shape of the graph and writes a short comment. The comment may say the pattern looks normal, that there is a sharp, narrow spike (a monoclonal band or M-spike), or that there is a broad, smooth rise or fall in one area. The size of each group is reported as its own result, and a measured spike is reported separately as M-protein.

Why it matters

SPEP is mainly used to look for a monoclonal protein, which is linked to conditions such as MGUS, multiple myeloma and Waldenström macroglobulinemia. It also shows broader patterns that can go along with inflammation, infection, liver or kidney disease, or low antibody levels. The comment describes a pattern and does not name a cause, and most patterns have several possible explanations. If the pattern looks monoclonal or unclear, labs often add immunofixation to confirm it. Your clinician reads the comment together with your symptoms and other tests.

What can affect your result

  • Inflammation, infection and injury, which raise the alpha-1 and alpha-2 groups and can lower albumin (acute phase pattern)
  • Liver disease, which can lower albumin and raise the gamma group
  • Protein loss through the kidneys (nephrotic syndrome), which can lower albumin and raise alpha-2
  • Pregnancy, which can lower albumin and raise alpha-1
  • Dehydration, which can raise albumin
  • Steroid medicines (higher alpha-2) and estrogen therapy (higher beta)
  • Monoclonal antibody medicines such as daratumumab, which can mimic a spike
  • Sample quality: hemolysis, fibrinogen in plasma and contrast dye can create false bands, and a serum sample is required
  • Monoclonal antibody medicines such as daratumumab, elotuzumab and isatuximab can look like a monoclonal band.
  • Hemolysis, fibrinogen (from a plasma sample), a high C-reactive protein, iodinated contrast dye and some antibiotics can create false peaks. ARUP rejects plasma and uses serum.
  • A broad rise in normal antibodies (polyclonal background) can hide a small monoclonal protein.
  • Pregnancy, steroid medicines, estrogen therapy and dehydration shift the normal fractions (see the factors below).
  • Some labs ask you to fast for up to 12 hours before the test (MedlinePlus); ARUP lists no patient preparation. Follow your lab's instructions.

Inflammation patterns can change over days to weeks as an illness settles. A monoclonal band changes slowly, over weeks to months.

When to talk to a clinician

A comment that mentions a monoclonal band or spike is worth a prompt conversation with the clinician who ordered the test, though it is not an emergency. Other patterns, such as a polyclonal increase or a low gamma group, usually call for follow-up at your next visit unless you feel unwell. Talk with your clinician soon about bone pain, a bone broken by a minor injury, tiredness or anemia with no clear cause, kidney problems, high calcium, or numbness and tingling with no other cause. Call your local emergency number for chest pain, trouble breathing, confusion or fainting.

Questions you could ask

  • What does the pattern in my report mean for me, and does it need follow-up?
  • Should I also have immunofixation or a free light chain test?
  • Could any illness, medicine or supplement I take explain this pattern?
  • When should we repeat this test?

Questions people ask

What does 'polyclonal increase in gamma globulins' mean?

It means the antibody group is raised, but the antibodies come from many different cells rather than one. This is a common reaction to infection, inflammation, autoimmune conditions or long-term liver disease, and it is not the same as a monoclonal spike. Your clinician can look at your symptoms and other results to find the reason.

My SPEP says there is no M-spike. Does that rule out a monoclonal protein?

Not completely. SPEP can miss small monoclonal proteins and often cannot see free light chains. If a condition is still suspected, clinicians commonly add immunofixation and a free light chain test, which are more sensitive.

Why was immunofixation added to my SPEP?

Some labs add it automatically when the SPEP pattern looks monoclonal or unclear. ARUP's SPEP-with-reflex test, for example, does this and does not add it when the pattern is normal or polyclonal. Immunofixation confirms whether a band is monoclonal and names its type, such as IgG kappa.

Show the science and sources

For clinicians and researchers

SPEP separates serum proteins by charge and size into albumin and the alpha-1, alpha-2, beta (beta-1 and beta-2) and gamma zones. Capillary zone electrophoresis has largely replaced agarose gel in modern labs (J Clin Med 2025). The alpha-1 zone is mostly alpha-1-antitrypsin; alpha-2 holds ceruloplasmin, alpha-2-macroglobulin and haptoglobin; beta-1 is mostly transferrin and beta-2 holds beta-lipoprotein with complement. Immunoglobulins mainly lie in gamma but can appear anywhere, and CRP lies between beta and gamma (AFP 2005). An M-protein is a sharp, well-defined band with a single heavy chain and a single light chain type, while a polyclonal gammopathy is a broad band with several heavy chains and both light chain types. A narrow band needs immunofixation or immunosubtraction to confirm that it is monoclonal. ARUP's SPEP-with-reflex test adds immunofixation when the pattern is monoclonal or suspicious and adds nothing when the pattern is normal, polyclonal or lacks a monoclonal band. SPEP is less sensitive than immunofixation (about 0.5–2 g/L versus 0.1–0.2 g/L; Ann Lab Med 2026), and free light chains are often invisible on SPEP. In one series cited by AFP, SPEP showed a spike in only 82% of people with multiple myeloma, so IMWG advises using SPEP with serum free light chains and either immunofixation or mass spectrometry. Causes of a polyclonal gamma increase include viral and bacterial infections, connective tissue disease, chronic liver disease and some cancers (AFP 2005, Table 3). Fraction reference intervals are method-specific; ARUP, for example, lists albumin 3.75–5.01, alpha-1 0.19–0.46, alpha-2 0.48–1.05, beta 0.48–1.10 and gamma 0.62–1.51 g/dL, and MedlinePlus lists somewhat different example ranges. Pseudo-peaks arise from hemolysis, fibrinogen, CRP, contrast agents, antibiotics and therapeutic monoclonal antibodies.

LOINC 12851-2 (primary), 49296-7, 49275-1. Specimen: serum.

Sources

  1. Protein Electrophoresis, Serum (test 0050640), ARUP Laboratories
  2. Protein Electrophoresis with Reflex to Immunofixation, Serum (test 2002109), ARUP Laboratories
  3. Understanding and Interpreting Serum Protein Electrophoresis, American Family Physician (2005)
  4. Protein electrophoresis - serum, MedlinePlus (National Library of Medicine)
  5. Multiple Myeloma Laboratory Diagnostics Made Simple: Practical Insights and Key Recommendations, Journal of Clinical Medicine (2025)
  6. Paradigm Shift in Monoclonal Protein Detection: From Electrophoresis-based to Mass Spectrometry-based Methods, Annals of Laboratory Medicine (2026)
  7. QMPSS - Overview: Monoclonal Protein Study, Quantitative, Serum, Mayo Clinic Laboratories (2025)

AI-verified against cited sources. Awaiting expert review. Last reviewed 2026-10-03. How we build and check these pages.

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