From the Guidelines
Slightly elevated globulin and protein levels in blood tests typically warrant monitoring rather than immediate intervention, as these elevations can result from various conditions ranging from mild inflammation to more serious disorders, such as autoimmune hepatitis, which is characterized by increased serum globulin or IgG levels in approximately 85% of patients 1. You should follow up with your healthcare provider for further evaluation, as these elevations can be caused by dehydration, infection, inflammation, or autoimmune conditions. Normal protein levels generally range from 6.0-8.3 g/dL, while globulin ranges from 2.0-3.5 g/dL. Mild elevations may be caused by temporary conditions like minor infections, and the body produces various globulins as part of immune function, with temporary increases occurring during normal immune responses, while persistent elevations may indicate underlying chronic conditions that require specific treatment. Some key points to consider in the evaluation of elevated globulin and protein levels include:
- The presence of high IgG levels is a distinctive feature of autoimmune hepatitis, with IgA and IgM levels usually being normal 1
- Elevated serum autoantibody titres, such as ANA or ASMA, may be encountered in patients with non-alcoholic fatty liver disease (NAFLD), but do not necessarily suggest autoimmune hepatitis, and should prompt further evaluation, including consideration of a liver biopsy 1
- The finding of autoantibody positivity associated with hypergammaglobulinemia should also prompt further evaluation, including consideration of a liver biopsy 1 While waiting for your follow-up appointment, maintain good hydration and report any symptoms like fatigue, unexplained weight loss, or joint pain. Your doctor may recommend additional tests, such as:
- Protein electrophoresis to determine specific protein fractions
- Liver function tests
- Tests for specific inflammatory markers
- Liver biopsy to evaluate for autoimmune hepatitis or other liver conditions 1
From the Research
Slightly High Globulin and Protein
- A slightly high globulin level can be an indicator of various health conditions, including liver disease 2, hypogammaglobulinaemia or hypergammaglobulinaemia 3, and inflammatory disease states 4.
- Calculated globulin fraction, derived from liver function tests, can be used as a screening tool for hypogammaglobulinaemia or paraproteins in hospitalized patients 3.
- Elevated serum globulin levels have been associated with a higher mortality risk in incident hemodialysis patients, independent of other markers of malnutrition and inflammation 4.
- Baseline liver function tests, including globulin levels, have been found to be associated with the progression of chronic kidney disease and renal outcomes in Aboriginal and Torres Strait Islander people 5.
Possible Causes
- Liver disease: Gc-globulin levels have been found to be reduced in liver disease, particularly in patients with acute liver failure 2.
- Inflammatory disease states: Serum globulin can be elevated in inflammatory disease states, which are common in hemodialysis patients 4.
- Hypogammaglobulinaemia or hypergammaglobulinaemia: Calculated globulin fraction can be used to identify patients with hypogammaglobulinaemia or hypergammaglobulinaemia 3.
- Chronic kidney disease: Baseline liver function tests, including globulin levels, have been found to be associated with the progression of chronic kidney disease and renal outcomes 5.
Associations
- Globulin levels have been found to be inversely associated with albumin levels in patients with liver disease 2.
- Elevated serum globulin levels have been associated with a higher mortality risk in incident hemodialysis patients 4.
- Low serum albumin and haemoglobin have been found to be associated with annual decline in eGFR and renal outcomes in Aboriginal and Torres Strait Islander people 5.