Globulin Levels in Multiple Myeloma
Yes, globulin levels are typically increased in multiple myeloma due to the overproduction of monoclonal immunoglobulins (M-protein) by clonal plasma cells. 1, 2
Understanding the Protein Pattern
Multiple myeloma is characterized by excessive production of a monoclonal immunoglobulin or its fragments, which appears as an abnormal protein spike in the globulin fraction on serum protein electrophoresis. 1, 3 This monoclonal protein (M-protein) is produced by the malignant plasma cell clone and accumulates in the serum, leading to elevated total globulin levels in most cases. 4, 5
Typical Laboratory Findings
- Serum protein electrophoresis demonstrates a discrete homogeneous peak (M-spike) in the gamma globulin region in approximately 83% of cases, most commonly IgG type (83.3%), followed by IgA type (16.7%). 3
- Total protein is often elevated due to the increased globulin fraction, while albumin may be normal or decreased. 1
- Quantitative immunoglobulin measurement by nephelometry shows marked elevation of one immunoglobulin class (IgG, IgA, or IgM) with suppression of the uninvolved immunoglobulins. 1
Important Caveats and Exceptions
When Globulin May NOT Be Elevated
Light chain-only myeloma (approximately 20% of cases) produces only free light chains that are rapidly cleared by the kidneys, resulting in minimal or no elevation of serum globulin despite active disease. 1, 6 These patients require serum free light chain assay for diagnosis and monitoring. 1
Non-secretory myeloma (approximately 3% of cases) produces no detectable monoclonal protein in serum or urine, resulting in normal or even low globulin levels. 1, 6 These cases are diagnosed by bone marrow examination showing ≥10% clonal plasma cells and evidence of end-organ damage. 1
Hypogammaglobulinemia can paradoxically occur in multiple myeloma when the malignant clone suppresses normal immunoglobulin production more severely than it produces M-protein, particularly in light chain and non-secretory variants. 6 This represents secondary immune deficiency and increases infection risk. 6
Clinical Significance of the Gamma Gap
The gamma gap (calculated as total protein minus albumin minus M-spike) serves as a useful prognostic marker. 3 An elevated gamma gap correlates strongly with M-spike levels and demonstrates high diagnostic accuracy (86.2%) in distinguishing pre- and post-treatment status in multiple myeloma patients. 3 This makes it a valuable tool for monitoring treatment response. 3
Diagnostic Approach
When evaluating suspected multiple myeloma with elevated globulin:
- Order serum protein electrophoresis to identify and quantify the M-spike, which appears as a discrete band typically in the gamma region. 1
- Perform immunofixation electrophoresis to characterize the specific heavy chain (IgG, IgA, IgM) and light chain (kappa or lambda) type of the monoclonal protein. 1
- Measure quantitative immunoglobulins by nephelometry, as this is complementary to electrophoresis and particularly useful for detecting suppression of uninvolved immunoglobulins. 1
- Include serum free light chain assay in all cases, as this is essential for detecting light chain-only myeloma and provides high sensitivity when combined with serum protein electrophoresis. 1
- Obtain 24-hour urine collection for protein electrophoresis and immunofixation to detect Bence Jones protein (urinary light chains), which may be present even when serum M-protein is low. 1
Common Pitfalls to Avoid
Do not rely solely on total protein or globulin levels to exclude multiple myeloma, as light chain and non-secretory variants may have normal or low globulin despite active disease requiring treatment. 1, 6
Do not assume elevated globulin always indicates multiple myeloma, as polyclonal hypergammaglobulinemia from chronic infections, autoimmune diseases, or liver disease produces a broad-based elevation rather than a discrete M-spike. 1
Do not use random urine samples instead of 24-hour urine collection for initial diagnosis, as proper quantitation of urinary M-protein requires an adequately concentrated 24-hour specimen. 1
Do not skip immunofixation even when protein electrophoresis appears normal, as small M-proteins may be missed by electrophoresis alone, particularly in light chain disease. 1