Immunofixation (IFE), Serum
Checks whether a protein made by one clone of plasma cells is in your blood. If so, it names the type, such as IgG kappa.
AI-verified against cited sources. Awaiting expert reviewAlso called IFE, sIFE, SIFELOINC 25700-6
What it is
Immunofixation (IFE) is a blood test that looks for a monoclonal protein, also called an M-protein or paraprotein. This is an antibody made by a single group of identical plasma cells. The lab first separates your blood proteins with an electric current. Then it adds antibodies that stick to each type of immunoglobulin (IgG, IgA, IgM) and to each type of light chain (kappa and lambda). A narrow, distinct band means a monoclonal protein is present, and the lab names it by its heavy and light chain, such as IgG kappa. Your result is a short written report, not a number. Some labs now use a mass spectrometry method (for example MASS-FIX) to answer the same question.
Why it matters
IFE is used with serum protein electrophoresis (SPEP) and a free light chain test when a clinician is looking at conditions such as MGUS, multiple myeloma, Waldenström macroglobulinemia or AL amyloidosis. It is more sensitive than SPEP, so it can find a small band that SPEP misses. Finding a monoclonal protein is not a diagnosis. It is fairly common in older adults and, most often, it is a condition called MGUS that causes no symptoms. The type of protein and its amount help your clinician decide how closely to follow it.
What can affect your result
- Age: monoclonal proteins become more common with age (MGUS is found in about 3% to 6% of adults over 50)
- Monoclonal antibody medicines, which can look like a monoclonal protein on this test
- The method used: gel immunofixation, capillary immunosubtraction and mass spectrometry differ in how small a band they can find
- Sample type: serum is the accepted sample (ARUP rejects plasma), and fibrinogen can create a false band on electrophoresis
- Hemolysis, contrast dye and some antibiotics, which can cause artifacts
- Recovery after a stem cell transplant, which can cause small temporary extra bands
- Monoclonal antibody medicines such as daratumumab, elotuzumab and isatuximab can appear as an extra band that looks like a patient's own monoclonal protein. Tell the lab and your clinician if you take one.
- ARUP rejects plasma for its protein electrophoresis tests, and fibrinogen is a known source of false bands on electrophoresis (J Clin Med 2025 review). A serum sample is used.
- Hemolyzed samples, iodinated contrast dye and some antibiotics can create artifacts on electrophoresis tests (J Clin Med 2025 review).
- Recovery after a stem cell transplant can cause small, temporary extra bands that are not a return of disease.
- Different methods (gel immunofixation, capillary immunosubtraction and mass spectrometry such as MASS-FIX) have different sensitivity, so a result from one method may not match another.
Not applicable to a one-time result. A monoclonal protein usually changes slowly, over weeks to months.
When to talk to a clinician
A monoclonal protein result deserves a follow-up conversation with the clinician who ordered the test. It is usually not an emergency. Talk with your clinician soon if you have a monoclonal protein and any of the following: bone pain or a bone broken by a minor injury, tiredness or anemia with no clear cause, kidney problems, high blood 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 type of monoclonal protein was found, and what does that type mean for follow-up?
- Do I need other tests, such as a free light chain test or a urine test?
- How often should this be rechecked, and should I use the same lab each time?
- Could any medicine I take, including a monoclonal antibody medicine, explain this band?
Questions people ask
What does 'IgG kappa' on my report mean?
It names the two parts of the antibody. IgG is the heavy chain type (the lab may also find IgA or IgM), and kappa is the light chain type (the other is lambda). Every antibody has one of each. A monoclonal protein has just one combination because it comes from one clone of plasma cells.
Does a monoclonal protein mean I have cancer?
Not necessarily. The most common reason is monoclonal gammopathy of undetermined significance (MGUS), found in about 3% to 6% of adults over 50. It does not cause symptoms, and about 1% of people with MGUS each year go on to develop myeloma or a related condition. Your clinician can use the protein type, its amount, a free light chain test and other results to decide how closely to follow it.
My SPEP showed no spike, but my IFE shows a band. Why?
IFE can find much smaller amounts of a monoclonal protein than SPEP can. A faint band can show up on IFE and be too small to see on SPEP. Both results can be correct, and your clinician can compare them with your other tests.
Show the science and sources
For clinicians and researchers
In immunofixation electrophoresis (IFE), serum proteins are separated on an agarose gel, then overlaid with monospecific antisera against IgG, IgA, IgM, kappa and lambda. A monoclonal immunoglobulin shows as a restricted band that lines up in one heavy chain lane and one light chain lane. IFE is qualitative; the amount is measured by SPEP densitometry or another method. Reported detection limits are about 0.1 g/L (0.01 g/dL) for IFE and about 1 g/L (0.1 g/dL) for SPEP (J Clin Med 2025), or 0.1–0.2 versus 0.5–2 g/L in another review (Ann Lab Med 2026). IMWG guidance says a monoclonal protein is adequately documented with SPEP, serum free light chains and either IFE or serum mass spectrometry. Immunosubtraction on capillary electrophoresis is automated and widely used, but it is less sensitive for small proteins and for free light chains and has no antisera for IgD or IgE, so gel IFE remains the reference method for equivocal cases and response assessment. Mayo MASS-FIX (immunoenrichment with MALDI-TOF mass spectrometry) has a limit of detection below 0.1 g/L, matched the IFE isotype in 98% of serum samples in one study, and can detect light chain glycosylation; Mayo describes it as more sensitive than IFE. Therapeutic antibodies such as daratumumab, elotuzumab and isatuximab can mimic an M-protein on IFE, and mass spectrometry or drug-specific IFE assays can tell them apart. Oligoclonal bands are common after stem cell transplantation.
LOINC 25700-6 (primary), 49275-1, 14895-7, 13348-8, 74665-1. Specimen: serum.
Sources
- Protein Electrophoresis with Reflex to Immunofixation, Serum (test 2002109), ARUP Laboratories
- Monoclonal Protein Study, Expanded Panel, Serum (test 2002715), ARUP Laboratories
- QMPSS - Overview: Monoclonal Protein Study, Quantitative, Serum, Mayo Clinic Laboratories (2025)
- Multiple Myeloma Laboratory Diagnostics Made Simple: Practical Insights and Key Recommendations, Journal of Clinical Medicine (2025)
- Paradigm Shift in Monoclonal Protein Detection: From Electrophoresis-based to Mass Spectrometry-based Methods, Annals of Laboratory Medicine (2026)
- Current risk stratification and staging of multiple myeloma and related clonal plasma cell disorders, Leukemia (2025)
AI-verified against cited sources. Awaiting expert review. Last reviewed 2026-10-03. How we build and check these pages.