Immunofixation Electrophoresis in Clinical Practice

Technical Methodology and Clinical Applications

Immunofixation electrophoresis (IFE) is a laboratory technique that identifies and characterizes specific proteins, particularly monoclonal immunoglobulins, by combining electrophoretic separation of proteins with immunoprecipitation using specific antisera against immunoglobulin heavy chains (IgG, IgA, IgM) and light chains (κ or λ), as recommended by the International Society of Nephrology 1, 2
IFE can be performed on serum, concentrated urine specimens, or other low-viscosity body fluids, and is essential for detecting small amounts of monoclonal immunoglobulin that may be missed by electrophoresis alone, according to the American Society of Clinical Oncology 1, 2

IFE is significantly more sensitive than standard protein electrophoresis (SPEP) and is essential for detecting small amounts of monoclonal immunoglobulin, with a detection rate of 100% in some studies, as reported by the National Comprehensive Cancer Network 1
IFE is necessary for definitive identification and typing of monoclonal immunoglobulins, determining complete response to treatment, and confirming the presence of monoclonal proteins when SPEP shows abnormal patterns, as recommended by the European Society for Medical Oncology 1, 3
Both serum and urine immunofixation should be performed because this combined approach is more sensitive than protein electrophoresis alone for detecting monoclonal proteins, according to the International Myeloma Society 1, 3

IFE is a fundamental component of the diagnostic workup for multiple myeloma, required to confirm the presence and type of monoclonal protein, as recommended by the American College of Physicians 2
Serum immunofixation may be more helpful than serum free light-chain assays in diseases associated with an intact monoclonal immunoglobulin, such as proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID), according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines 1, 3
IFE should be performed even if there is no measurable protein and even if there is no peak on urine electrophoresis, as some cases produce only small amounts of monoclonal protein, as recommended by the European Renal Association 2

Order serum and urine IFE when SPEP shows an abnormal pattern, monoclonal spike, or when there is strong clinical suspicion of plasma cell disorder even with normal SPEP, as recommended by the American Society of Hematology 1, 5
In patients with unexplained peripheral neuropathy, renal dysfunction with proteinuria, or systemic symptoms suggesting plasma cell disorder, order IFE as part of initial screening, according to the European Federation of Neurological Societies 1, 6
For monitoring known monoclonal gammopathies, IFE is essential for determining complete response, as it can detect residual disease not visible on standard electrophoresis, as recommended by the International Society of Nephrology 1, 3