From the Guidelines
Hyperglobulinemia is a strong indicator of autoimmune hepatitis (AIH).
Key Features of Hyperglobulinemia in AIH
- Increased serum globulin or IgG levels are found in approximately 85% of patients with AIH, even in the absence of cirrhosis 1
- The presence of high IgG levels is a very distinctive feature, with IgA and IgM levels usually normal 1
- A selectively elevated IgG in the absence of IgA and IgM elevation is particularly suggestive of AIH 1
Diagnostic Criteria
- The simplified diagnostic criteria for AIH include increased IgG or γ-globulins level, with a score of +1 for levels above the upper limit of normal and +2 for levels above 1.1x the upper limit of normal 1
- The level of immunoglobulins is an important and useful marker in monitoring the response to treatment and the achievement of remission, with normalization of both transaminase levels and IgG levels considered a diagnostic marker of full biochemical remission 1
From the Research
Hyperglobulinemia Indications
Hyperglobulinemia can indicate various conditions, including:
- Liver disease, as it is related to a common dysfunction estimated by ICG clearance, which represents mainly the liver's blood flow and removal capacity 2
- Immune dysregulation or inflammation, as it can be caused by liver disease, immune dysregulation, or inflammation 3
- Inflammatory bowel disease (IBD), as a high globulin fraction may function independently of albumin as a biomarker of disease severity in IBD patients over a multiyear period 4
- Haematological malignancy, autoimmune disease, or infections, as significantly elevated calculated globulin were seen in patients with these conditions 5
- Monoclonal gammopathy, as pseudohyperphosphatemia may suggest the need for an evaluation to rule out the presence of a monoclonal gammopathy 6
Associated Conditions
Hyperglobulinemia can be associated with:
- Hypogammaglobulinaemia or paraproteins, as calculated globulin fraction can identify patients with these conditions 5
- IgG4-related disease, as the presence of markedly elevated serum IgG4 concentrations is around 90% specific for diagnosing this disease 3
- Hyperviscosity, as polyclonal hypergammaglobulinaemia can lead to this condition, requiring plasmapheresis 3
Diagnostic Considerations
When diagnosing hyperglobulinemia, it is essential to consider:
- The correlation between serum globulin level and liver function tests, such as ICG clearance 2
- The measurement of serum concentrations of C-reactive protein and IgG subclasses to help diagnose the underlying condition 3
- The potential for pseudohyperphosphatemia in patients with hyperglobulinemia, which can falsely elevate serum inorganic phosphate levels 6