From the Guidelines
A workup for high globulin levels should begin with a comprehensive history and physical examination, followed by specific laboratory tests to determine the underlying cause, including serum protein electrophoresis (SPEP), immunofixation electrophoresis, and quantitative immunoglobulin levels (IgG, IgA, IgM) as recommended by the most recent guidelines 1. The initial evaluation should also include a complete blood count, comprehensive metabolic panel, and inflammatory markers like ESR and CRP.
- If monoclonal gammopathy is detected, additional tests such as free light chain assay, bone marrow biopsy, and skeletal survey may be necessary to rule out multiple myeloma or related disorders.
- For polyclonal elevations, focus on identifying chronic inflammatory conditions, autoimmune diseases, or chronic infections by ordering appropriate autoimmune panels (ANA, RF, anti-CCP), viral serologies (HIV, hepatitis), or specific tests based on clinical suspicion.
- Liver function tests are important as chronic liver disease can cause hyperglobulinemia. The workup should be tailored to the patient's clinical presentation, as high globulin levels can result from various conditions including multiple myeloma, autoimmune disorders, chronic infections, and liver disease, each requiring different management approaches, and the use of serum free light chain (FLC) assay along with serum protein electrophoresis and serum immunofixation electrophoresis yields high sensitivity while screening for MM and related plasma cell disorders 1.
- The FLC assay cannot replace the 24-hour urine protein electrophoresis for monitoring patients with measurable urinary M-proteins.
- Bone marrow aspiration and biopsy are recommended to detect quantitative and/or qualitative abnormalities of bone marrow plasma cells.
- To evaluate lytic bone lesions, full skeleton radiographic survey or whole-body, low-dose CT is recommended.
- Chromosome analysis by metaphase cytogenetics and fluorescence in situ hybridization (FISH) should be performed with the plasma cells obtained from bone marrow aspiration to identify specific chromosomal abnormalities involving translocations, deletions, or amplifications. The most recent guidelines from 2017 1 provide the best approach for the workup of elevated globulin levels, and should be followed to ensure accurate diagnosis and management.
From the Research
Workup for Elevated Globulin Levels
The workup for elevated globulin levels involves several steps to determine the underlying cause of the elevation.
- Serum protein electrophoresis (SPEP) is used to identify and quantify the type of protein present in the blood 2.
- The results of SPEP can help differentiate between monoclonal and polyclonal gammopathies, with monoclonal gammopathies indicating a clonal process that is malignant or potentially malignant 2.
- A bone marrow biopsy is often necessary to confirm the diagnosis of multiple myeloma or other plasma cell disorders 2, 3.
- Immunofixation electrophoresis (IFE) or immunosubtraction (ISUB) may also be used to further characterize the type of protein present in the blood 4.
- Other tests, such as complete blood counts, blood chemistry tests, and imaging studies, may also be ordered to evaluate the patient's overall health and to look for any signs of end-organ damage 3.
Interpretation of Results
The interpretation of the results of these tests requires careful consideration of the patient's clinical presentation and medical history.
- A homogeneous spike-like peak in a focal region of the gamma-globulin zone on SPEP indicates a monoclonal gammopathy 2.
- The quantity of M protein, the results of bone marrow biopsy, and other characteristics can help differentiate multiple myeloma from other causes of monoclonal gammopathy 2.
- The presence of an elevated globulin level, particularly if it is associated with other symptoms such as hypercalcemia, anemia, or renal impairment, should prompt further evaluation for multiple myeloma or other plasma cell disorders 3.
Clinical Correlations
Elevated globulin levels can be associated with a variety of clinical conditions, including: