What is the sensitivity of Serum Protein Electrophoresis (SPEP) for diagnosing Monoclonal Gammopathy of Undetermined Significance (MGUS)?

Sensitivity of SPEP for MGUS Diagnosis

Serum protein electrophoresis (SPEP) alone has a sensitivity of approximately 91% for detecting monoclonal gammopathies including MGUS, but when combined with serum free light chain (FLC) assay, the sensitivity increases to 95%. 1

Diagnostic Testing for MGUS

• SPEP is a first-line test that identifies monoclonal proteins as homogeneous spike-like peaks in the gamma-globulin zone, but has limitations in detecting small monoclonal proteins 2
• Serum immunofixation electrophoresis (SIFE) is more sensitive than SPEP and necessary for identification and typing of monoclonal immunoglobulins, even when SPEP appears negative 2
• The serum FLC assay significantly improves detection of monoclonal gammopathies when used alongside SPEP and SIFE, particularly for light chain disorders 3
• The combination of SPEP and FLC assay provides 95% sensitivity (95% CI: 89-99%) and 99% specificity (95% CI: 96-100%) for diagnosing monoclonal gammopathies 1

Limitations of SPEP in MGUS Detection

• SPEP alone may miss small monoclonal proteins that are below its detection threshold, particularly in early MGUS 2
• Approximately 3% of patients with plasma cell disorders have non-secretory disease with neither serum nor urine proteins detectable by conventional electrophoresis 3
• Light chain MGUS may be missed by SPEP alone, as these patients have abnormal free light chain ratios without detectable M-proteins on SPEP 3
• MGUS with very low M-protein concentration (<5 g/L) may be difficult to detect reliably with SPEP alone 4

Recommended Diagnostic Approach

• The optimal diagnostic panel for suspected monoclonal gammopathies should include SPEP, SIFE, and serum FLC assay 3, 2
• 24-hour urine protein electrophoresis (UPEP) and urine immunofixation electrophoresis (UIFE) are recommended as complementary studies to detect Bence Jones proteinuria 3
• Bone marrow examination is not routinely recommended for asymptomatic patients with apparent IgG MGUS if the serum M-protein is ≤15 g/L and there is no end-organ damage 3
• For IgA and IgM M-proteins, bone marrow examination should be part of the diagnostic workup regardless of concentration 3

Clinical Implications and Follow-up

• MGUS is found in approximately 3% of people older than 70 years and in at least 1% of those aged over 50 5
• Long-term follow-up is essential as approximately 1% of MGUS patients per year will progress to multiple myeloma or related malignancies 5
• Serial monitoring of M-protein concentration is important, with a reference change value (RCV) of approximately 37-40% indicating a significant change that may warrant clinical attention 4
• When interpreting FLC results, renal function must be considered as it affects free light chain levels and ratios 2

Common Pitfalls in MGUS Diagnosis

• Failing to perform SIFE when clinical suspicion is high but SPEP is negative 2
• Not including serum FLC assay in the initial workup, which can miss light chain disorders 3
• Using different FLC assays for serial monitoring (different assays are not mathematically convertible) 2
• Confusing polyclonal increases in immunoglobulins (broad-based elevation) with monoclonal gammopathies (discrete peaks) on SPEP 6