From the Guidelines
Increased gamma globulin levels are a non-specific finding that can be associated with various conditions, including infections, autoimmune disorders, and certain blood cancers, and the most recent and highest quality study suggests that the management of increased gamma globulin levels should focus on identifying and treating the underlying cause, rather than the elevated levels themselves 1. The presence of elevated gamma globulin levels can be an indicator of an underlying immune system response, and it is essential to investigate the cause of this elevation to provide appropriate treatment.
- The differential diagnosis for increased gamma globulin levels is broad and includes chronic infections, autoimmune disorders like rheumatoid arthritis or lupus, liver diseases such as cirrhosis, and certain blood cancers like multiple myeloma.
- Diagnostic follow-up should include a complete blood count, comprehensive metabolic panel, and possibly serum protein electrophoresis to identify specific immunoglobulin patterns.
- In cases of significant elevation, immunofixation electrophoresis may be needed to rule out monoclonal gammopathy, as suggested by the European Myeloma Network 1.
- The immune system produces these proteins as part of its defense mechanism, so elevated levels reflect ongoing immune activity, and while mild elevations may be benign, persistent or significant increases warrant investigation to identify and address the underlying condition causing this immunological response.
- According to the most recent study, monitoring of serum immunoglobulin levels and use of intravenous immunoglobulin replacement is recommended in patients with hypogammaglobulinemia and recurrent or severe infections to reach a target trough of 600–800 mg/dL and improve clinical outcomes 1.
- The study also suggests that subcutaneous immunoglobulin therapy (SCIg) may be a useful therapeutic option in patients with hypogammaglobulinemia, with a significant reduction in infectious episodes and improvement in quality of life 1.
From the Research
Increased Gamma Globulin
- Increased gamma globulin, also known as hypergammaglobulinemia, can be caused by various factors, including liver disease, immune dysregulation, or inflammation 2
- It can also be a diagnostic clue for rare diseases such as histiocyte disorders, autoimmune lymphoproliferative syndrome, Castleman disease, and IgG4-related disease 2
- Measuring serum concentrations of C-reactive protein and IgG subclasses can be helpful in diagnosis, and IL-6-mediated inflammation can be an important driver of polyclonal hypergammaglobulinemia in some cases 2
Causes of Hypergammaglobulinemia
- Causes of polyclonal hypergammaglobulinemia can be divided into eight categories:
- Liver disease
- Autoimmune disease and vasculitis
- Infection and inflammation
- Non-haematological malignancy
- Haematological disorders
- IgG4-related disease
- Immunodeficiency syndromes
- Iatrogenic (from immunoglobulin therapy) 2
- Significantly elevated calculated globulin can be seen in patients with liver disease, haematological malignancy, autoimmune disease, or infections 3
Diagnosis and Management
- Calculated globulin fraction can be used as a screening tool for hypogammaglobulinaemia or paraproteins in hospitalized patients 3
- Managing polyclonal hypergammaglobulinemia typically involves treating the underlying condition, although rare cases may require plasmapheresis to prevent hyperviscosity 2
- Entecavir, an antiviral agent, has been shown to be effective in treating chronic hepatitis B virus infection, which can be a cause of hypergammaglobulinemia 4, 5