From the Guidelines
An elevated gamma region in electrophoresis is primarily correlated with increased immunoglobulin production, which can indicate several clinical conditions, most commonly suggesting monoclonal gammopathies such as multiple myeloma, monoclonal gammopathy of undetermined significance (MGUS), Waldenström's macroglobulinemia, or certain lymphomas, as supported by the most recent guidelines 1. This finding may also indicate polyclonal gammopathies seen in chronic inflammatory conditions, autoimmune disorders like rheumatoid arthritis or lupus, chronic infections, or liver diseases such as cirrhosis. The pattern of elevation is important - a sharp, narrow spike (M-spike) suggests a monoclonal process requiring further investigation with immunofixation electrophoresis, while a broader elevation indicates polyclonal gammopathy. When encountering an elevated gamma region, clinicians should consider the patient's complete clinical picture and pursue additional testing such as serum free light chain assays, bone marrow biopsy, or imaging studies as appropriate to determine the underlying cause, as recommended by recent clinical practice guidelines 1. The distinction between monoclonal and polyclonal patterns is crucial as monoclonal gammopathies may require hematology/oncology consultation for potential malignancy evaluation. Key considerations include:
- The use of serum free light chain (FLC) assay along with serum protein electrophoresis (SPEP) and serum immunofixation electrophoresis (SIFE) for high sensitivity in screening for multiple myeloma and related plasma cell disorders 1.
- The importance of bone marrow studies, including chromosome analysis by conventional karyotyping and fluorescence in situ hybridization (FISH), for identifying genetic and molecular subtypes of the disease 1.
- The role of imaging studies, such as full skeletal radiographic survey, for evaluating lytic bone lesions 1. Given the complexity and potential severity of conditions associated with an elevated gamma region, it is essential to approach each case with a comprehensive diagnostic workup and consideration of the latest clinical guidelines 1.
From the Research
Elevated Gamma Region Correlation
The elevated gamma region in electrophoresis labs is correlated with several conditions, including:
- Monoclonal gammopathies, which are associated with a clonal process that is malignant or potentially malignant, including multiple myeloma, Waldenstrom's macroglobulinemia, solitary plasmacytoma, smoldering multiple myeloma, monoclonal gammopathy of undetermined significance, plasma cell leukemia, heavy chain disease, and amyloidosis 2
- Polyclonal gammopathies, which may be caused by any reactive or inflammatory process, such as liver disease, immune dysregulation, or inflammation 3
- Autoimmune disorders, where high dose intravenous gammaglobulins have been used as a therapeutic tool 4
Underlying Conditions
The elevated gamma region can be caused by various underlying conditions, including:
- Liver disease
- Autoimmune disease and vasculitis
- Infection and inflammation
- Non-haematological malignancy
- Haematological disorders
- IgG4-related disease
- Immunodeficiency syndromes
- Iatrogenic (from immunoglobulin therapy) 3
Therapeutic Uses
Immune gamma globulin has been used therapeutically in various immune deficiency and autoimmune disorders, with a long history of treatment and expanding disease indications 5