What is the difference between Serum Immunofixation Electrophoresis (SIFE) and quantitative immunoglobulins?

Difference Between SIFE and Quantitative Immunoglobulins

Serum Immunofixation Electrophoresis (SIFE) identifies and characterizes the specific type of monoclonal protein present (which immunoglobulin heavy chain and light chain), while quantitative immunoglobulins measure the total concentration of each immunoglobulin class (IgG, IgA, IgM) in the blood, including both normal polyclonal and abnormal monoclonal proteins. 1

Purpose and Function

SIFE (Serum Immunofixation Electrophoresis)

• SIFE is a qualitative test that confirms the presence of a monoclonal protein (M-protein) and identifies its exact type by determining which specific immunoglobulin heavy chain (IgG, IgA, or IgM) and light chain (kappa or lambda) is being produced by the abnormal plasma cell clone 1, 2
• SIFE combines electrophoretic separation of serum proteins with immunoprecipitation using targeted antisera to identify specific immunoglobulin components 2
• This test is essential for phenotyping monoclonal gammopathies and is considered the reference method for confirmation when an abnormal pattern is detected on serum protein electrophoresis 2
• SIFE demonstrates superior sensitivity to standard protein electrophoresis, achieving 100% detection of monoclonal gammopathies in recent studies compared to 69.6% detection by electrophoresis alone 2

Quantitative Immunoglobulins

• Quantitative immunoglobulin testing measures the total amount of each major immunoglobulin class (IgG, IgA, IgM) present in serum, expressed in g/L or mg/dL 3
• In normal serum, approximately 80% is IgG, 15% is IgA, and 5% is IgM 3
• These measurements include both normal polyclonal immunoglobulins and any abnormal monoclonal protein that may be present, making it impossible to distinguish between the two based on quantitative testing alone 4
• Quantitative testing is performed using immunonephelometry or similar techniques 4

Clinical Application in Plasma Cell Disorders

Complementary Roles

• The National Comprehensive Cancer Network recommends both tests as part of the initial diagnostic workup for suspected plasma cell disorders, as they provide different but complementary information 5, 1
• When SPEP shows an abnormal pattern, follow-up testing should include both SIFE for characterization and quantitative immunoglobulin levels 1

Diagnostic Workflow

• SIFE answers "what type" of monoclonal protein is present (e.g., IgG kappa, IgA lambda), which is critical for diagnosis and classification 1, 2
• Quantitative immunoglobulins answer "how much" of each immunoglobulin class is present and can reveal immune paresis (suppression of normal immunoglobulins) 1, 3
• Visual assessment of normal immunoglobulin levels in the presence of a monoclonal gammopathy was correct in only 58% of cases, making quantitative testing by nephelometry essential 4

Key Clinical Distinctions

Detection of Immune Paresis

• Quantitative immunoglobulins are superior for detecting suppression of uninvolved immunoglobulin classes, which is an important prognostic feature in multiple myeloma 1
• For example, a patient with IgG myeloma may have elevated total IgG (due to the monoclonal protein) but suppressed IgA and IgM levels, which can only be appreciated through quantitative testing 1

Monitoring Disease

• Both tests are used for surveillance, with quantitative immunoglobulins plus quantitation of M-protein recommended at least every 3 months in patients with active myeloma 5
• SIFE is repeated as clinically indicated to confirm the persistence or disappearance of the monoclonal protein during treatment 5

Common Pitfalls

• Do not rely on quantitative immunoglobulins alone to diagnose monoclonal gammopathies, as they cannot distinguish between polyclonal and monoclonal increases 4
• SIFE is required even when quantitative immunoglobulins appear normal, as approximately 15-20% of myeloma cases produce only light chains that may not significantly elevate total immunoglobulin levels 1
• In cases with strong clinical suspicion of multiple myeloma, SIFE should be performed even if standard protein electrophoresis appears normal, as SIFE has superior sensitivity 2