From the Guidelines
The primary blood tests used to screen for Monoclonal Gammopathy of Undetermined Significance (MGUS) include serum protein electrophoresis (SPEP), immunofixation electrophoresis (IFE), and serum free light chain assay (sFLC). These tests are essential for detecting and characterizing the monoclonal protein (M-protein) associated with MGUS. SPEP is the initial test that identifies the presence of an M-protein spike, which is characteristic of MGUS. If an M-protein is detected, immunofixation electrophoresis is then performed to determine the specific type of immunoglobulin involved (IgG, IgA, IgM, IgD, or IgE) and whether it contains kappa or lambda light chains. The serum free light chain assay measures the levels of unbound light chains in the blood and calculates the kappa/lambda ratio, which helps detect light chain abnormalities that might be missed by SPEP alone.
Key Tests for MGUS Screening
- Serum protein electrophoresis (SPEP)
- Immunofixation electrophoresis (IFE)
- Serum free light chain assay (sFLC)
- Complete blood count (CBC) to assess for cytopenias
According to the most recent and highest quality study 1, the serum free light-chain (FLC) assay along with serum analyses (SPEP and SIFE) yields high sensitivity while screening for MM and related plasma cell disorders, including MGUS. The FLC assay is also helpful in prognostication of MGUS and allows for quantitative monitoring of patients with light chain amyloidosis and light chain myeloma.
Early detection of MGUS is important as it requires monitoring due to its potential progression to multiple myeloma, Waldenström macroglobulinemia, or related disorders at a rate of approximately 1% per year. The tests mentioned above are crucial for the differential diagnosis between MGUS, smoldering myeloma, and multiple myeloma, as outlined in the guidelines 1.
From the Research
MGUS Screening Blood Tests
To screen for Monoclonal Gammopathy of Undetermined Significance (MGUS), several specific blood tests are utilized. These include:
- Serum protein electrophoresis (SPEP) to identify and quantify the monoclonal protein (M-protein) in the blood 2, 3
- Immunofixation electrophoresis to determine the type of M-protein (IgG, IgA, or IgM) 2, 3
- Serum free light chain assay (SFLCA) to measure the levels of free light chains (κ and λ) in the blood 4, 3
- κ/λ ratio to assess the balance between κ and λ light chains 4
Interpretation of Test Results
The results of these tests are used to diagnose and monitor MGUS. However, it is essential to note that:
- A normal κ/λ ratio does not exclude MGUS, and an abnormal ratio is not diagnostic of MGUS 4
- The false negative rate for κ/λ ratio is higher in samples with lambda chains and in patients with MGUS, smoldering myeloma, and multiple myeloma 4
- Electrophoretic studies of serum and urine are superior to SFLCA and κ/λ ratio for diagnosing and monitoring MGUS 4
Risk Stratification
Patients with MGUS can be risk-stratified based on the amount and type of their monoclonal protein, as well as the presence of an abnormal light-chain ratio 5, 3. This risk stratification is crucial for determining the likelihood of progression to multiple myeloma or related disorders. The size and type of M protein, the number of bone marrow plasma cells, and the results of the FLC ratio are independent risk factors for progression 3.