From the Guidelines
Elevated immunoglobulin G (IgG) levels are a distinctive feature of autoimmune hepatitis (AIH), particularly when selectively elevated in the absence of IgA and IgM elevation, as noted in the EASL clinical practice guidelines 1. When IgG levels are found to be raised, further investigation is warranted to determine the underlying cause, with AIH being a key consideration. Common conditions associated with elevated IgG include chronic hepatitis, autoimmune disorders like rheumatoid arthritis and lupus, multiple myeloma, and chronic inflammatory conditions. The pattern of elevation can provide diagnostic clues - polyclonal elevation (all IgG subtypes increased) typically suggests chronic inflammation or infection, while monoclonal elevation (one IgG subtype increased) raises concern for plasma cell disorders like multiple myeloma. Management depends entirely on identifying and treating the underlying cause rather than treating the elevated IgG itself, with the EASL guidelines providing a framework for diagnosis and treatment of AIH 1. Additional testing often includes specific antibody panels, protein electrophoresis, imaging studies, and sometimes tissue biopsies, as outlined in the guidelines. IgG elevation should be interpreted in clinical context, as levels can vary with age, and mild elevations may occasionally be seen in otherwise healthy individuals, particularly the elderly. Key points to consider in the evaluation of elevated IgG levels include:
- The presence of other autoimmune antibodies, such as ANA or SMA, which can support a diagnosis of AIH 1
- The pattern of IgG elevation, with selectively elevated IgG being more suggestive of AIH 1
- The presence of chronic hepatitis or other inflammatory conditions, which can also cause elevated IgG levels 1
- The need for careful interpretation of IgG levels in clinical context, taking into account age and other factors that can influence IgG levels.
From the Research
Raised Immunoglobulin G and Mortality Risk
- Elevated levels of immunoglobulin G (IgG) have been associated with an increased risk of total and cause-specific mortality, as seen in the Vietnam Experience Study 2.
- The study found that higher IgG concentrations were positively related to all-cause mortality, with a hazard ratio (HR) of 5.8 per standard deviation increase in IgG levels.
- Similarly, IgG was also associated with an increased risk of mortality from "other" causes, mainly infectious disease, with an HR of 33.4 per standard deviation increase in IgG levels.
Raised Immunoglobulin G in Chronic Liver Disease
- Elevated serum IgG levels have been observed in patients with chronic liver disease (CLD), particularly those with decompensated cirrhosis 3.
- The study found that patients with CLD and decompensated cirrhosis had significantly higher serum IgG levels compared to those with compensated CLD.
- Elevated IgG levels in CLD patients may signal subclinical disease or be a marker of advanced liver disease.
Clinical Interpretation and Management of Polyclonal Hypergammaglobulinaemia
- Polyclonal hypergammaglobulinaemia, characterized by elevated levels of IgG, can be caused by various conditions, including liver disease, immune dysregulation, and inflammation 4.
- Measuring serum concentrations of C-reactive protein and IgG subclasses can be helpful in diagnosis.
- Managing polyclonal hypergammaglobulinaemia typically involves treating the underlying condition, although rare cases may require plasmapheresis to reduce hyperviscosity.
Immunoglobulin G and Autoimmune Diseases
- IgG-mediated activation of complement and IgG Fc receptors can drive severe and harmful inflammation in autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis 5.
- The cross-talk between complement and FcγRs is important in regulating the inflammatory response in autoimmune diseases.
- Serum IgG subclass levels can vary among different autoimmune diseases, with distinct characteristics observed in primary Sjogren syndrome, systemic sclerosis, and primary biliary cirrhosis 6.