From the Guidelines
A mild elevation of total globulin on routine lab testing is often a nonspecific finding that may not require immediate intervention but warrants clinical correlation, as it can be associated with various conditions including chronic inflammation, infections, liver disease, autoimmune disorders, and certain hematologic conditions 1. The significance of a mild elevation of total globulin depends on the degree of elevation, associated symptoms, and other laboratory abnormalities.
- Mild elevations (typically up to 4-4.5 g/dL) can occur in various conditions, and the globulin fraction consists of different proteins including immunoglobulins, which may reflect increased production of these proteins in response to underlying pathology.
- When encountering mildly elevated globulins, clinicians should review the patient's medical history, assess for symptoms, and consider the albumin/globulin ratio, which normally is greater than 1.
- If the elevation persists or increases on repeat testing, further investigation may be warranted, including protein electrophoresis to characterize the specific globulin fractions involved, as seen in autoimmune hepatitis where increased serum c-globulin or IgG levels are found in approximately 85% of patients 1. This can help distinguish between polyclonal elevations (suggesting inflammatory or infectious processes) and monoclonal elevations (raising concern for plasma cell disorders like multiple myeloma).
- In asymptomatic patients with stable mild elevations, periodic monitoring may be sufficient without immediate additional testing, but it is essential to consider the range within which c-globulins and IgGs are considered normal, as a proportion of patients may show apparently ‘‘normal’’ IgG levels at diagnosis, but still have a relative increase of their IgG levels considering their very low natural IgG levels 1.
From the Research
Significance of Mild Elevation of Total Globulin
- A mild elevation of total globulin on routine lab tests can be an indicator of various underlying conditions, including liver disease, immune dysregulation, or inflammation 2.
- Polyclonal hypergammaglobulinaemia, a condition characterized by an increase in globulin levels, can be caused by several factors, including liver disease, autoimmune disease, infection, and non-haematological malignancy 2.
- Measuring serum concentrations of C-reactive protein and IgG subclasses can be helpful in diagnosing the underlying cause of elevated globulin levels 2.
- In some cases, mildly elevated serum IgG4 concentrations can be seen in various conditions, making it essential to consider other diagnostic factors 2.
- Elevated liver enzymes, such as alanine aminotransferase and aspartate aminotransferase, can also be associated with increased risks of liver-related and all-cause mortality 3.
- A comprehensive evaluation, including medical history, physical examination, and laboratory tests, is necessary to determine the etiology of abnormal liver test results and elevated globulin levels 3.