From the Guidelines
Elevated globulin levels, specifically hyperglobulinemia, require immediate attention and further investigation to determine the underlying cause, as they can be associated with various conditions, including infections, autoimmune disorders, and certain cancers, which can significantly impact morbidity, mortality, and quality of life. The implications of elevated globulins can be far-reaching, affecting multiple organ systems and leading to complications such as hyperviscosity syndrome, neuropathy, and amyloidosis, as seen in Waldenström's macroglobulinaemia 1. Common causes of elevated globulins include chronic inflammation, infections like hepatitis or HIV, autoimmune disorders such as lupus or rheumatoid arthritis, and certain cancers, particularly multiple myeloma.
To determine the underlying cause of elevated globulins, additional tests are necessary, including:
- Protein electrophoresis
- Immunofixation
- Specific tests for suspected conditions, such as viral serology for hepatitis B and C viruses (HBV and HCV) and human immunodeficiency virus (HIV) 1
- Urine protein electrophoresis and/or urine immunofixation for exclusion of abnormal renal Ig secretion 1
- Testing for cold agglutinins and cryoglobulins, especially in patients with symptoms or laboratory evidence suggestive of their presence 1
While waiting for further evaluation, it is essential to maintain good general health practices, including:
- Adequate hydration
- Balanced nutrition
- Regular follow-up with a healthcare provider
Globulins are crucial proteins that include antibodies (immunoglobulins) which fight infections and other proteins involved in inflammation and immune function. Their elevation typically signals that the body's immune system is responding to something, but determining what is triggering this response is essential for appropriate management. In some cases, elevated globulins can be associated with specific conditions, such as autoimmune hepatitis, where increased serum c-globulin or IgG levels are found in approximately 85% of patients 1.
In the context of Waldenström's macroglobulinaemia, elevated IgM levels can lead to hyperviscosity syndrome, which requires prompt treatment with options such as plasmapheresis or rituximab-based therapy 1. Additionally, neuropathy is a common complication in patients with Waldenström's macroglobulinaemia, and evaluation by a neurologist and specialized neurological testing, including electromyography/nerve conduction studies, may be necessary 1.
Overall, elevated globulin levels require a comprehensive evaluation to determine the underlying cause and guide appropriate management, with the goal of improving morbidity, mortality, and quality of life.
From the Research
Implications of Elevated Globulins
Elevated globulins, specifically hyperglobulinemia, can have several implications for an individual's health. Some of the key implications include:
- Liver disease: Hyperglobulinemia is frequently detected in severe chronic liver diseases, such as liver cirrhosis, and may represent a functional aspect of the liver 2.
- Immune dysregulation: Polyclonal hypergammaglobulinaemia can be caused by immune dysregulation, inflammation, or liver disease, and can provide an important diagnostic clue for rare diseases such as histiocyte disorders or autoimmune lymphoproliferative syndrome 3.
- Increased risk of venous thromboembolism: Elevated serum gamma globulin levels (>27 g/L) have been identified as a risk factor for venous thromboembolism in patients with multiple myeloma 4.
- Antibody deficiency: Low levels of calculated globulin can be used as a screening test for antibody deficiency, and can detect both primary and secondary antibody deficiency 5.
- Hypogammaglobulinaemia or paraproteins: Calculated globulin can be used as a screening tool for hypogammaglobulinaemia or paraproteins in hospitalized patients, and can identify patients with significantly elevated or decreased immunoglobulin levels 6.
Clinical Interpretation
The clinical interpretation of elevated globulins depends on the underlying cause and the individual's overall health. Some key considerations include:
- Liver function: Hyperglobulinemia may be related to a common dysfunction estimated by ICG clearance, which represents mainly the liver's blood flow and removal capacity 2.
- Inflammation: IL-6-mediated inflammation can be an important driver of polyclonal hypergammaglobulinaemia in some cases 3.
- Immunoglobulin levels: Measuring serum concentrations of C-reactive protein and IgG subclasses can be helpful in diagnosis 3.
- Risk of venous thromboembolism: Patients with elevated serum gamma globulin levels should be monitored for an increased risk of venous thromboembolism 4.
Management
The management of elevated globulins depends on the underlying cause and the individual's overall health. Some key considerations include:
- Treating the underlying condition: In most cases, managing polyclonal hypergammaglobulinaemia simply involves treating the underlying condition 3.
- Monitoring for complications: Patients with elevated globulins should be monitored for complications such as venous thromboembolism or hyperviscosity 3, 4.
- Screening for antibody deficiency: Low levels of calculated globulin can be used as a screening test for antibody deficiency, and can detect both primary and secondary antibody deficiency 5.