From the Guidelines
Polyclonal gammopathy is a condition that should be managed by addressing the underlying cause, such as chronic infections, autoimmune diseases, or liver diseases, rather than the gammopathy itself, as recommended by the most recent study 1.
Causes and Treatment
Polyclonal gammopathy is characterized by increased production of multiple immunoglobulin classes by different plasma cell clones, and is typically a reactive process rather than a primary blood disorder. Common causes include:
- Chronic infections (like hepatitis, HIV, or tuberculosis)
- Autoimmune diseases (such as rheumatoid arthritis or lupus)
- Liver diseases (cirrhosis)
- Chronic inflammatory conditions Treatment focuses on addressing the underlying cause, such as:
- Antibiotics for infections
- Immunosuppressants for autoimmune conditions
- Supportive care for liver disease
Laboratory Findings
Laboratory findings typically show:
- Elevated total protein
- Increased gamma fraction on serum protein electrophoresis with a broad-based or diffuse pattern (rather than a sharp spike seen in monoclonal conditions)
- Normal calcium levels Regular monitoring is important, but polyclonal gammopathy itself is generally not dangerous - the primary concern is identifying and treating the underlying condition that triggered the immune response, as noted in the study 1.
Diagnosis and Management
In cases of complement-dominant MPGN, a search for a paraprotein should be considered, and serum and urine immunoelectrophoresis and immunofixation as well as a serum free light chain analysis may be recommended, as suggested by Beck Jr et al in the study 1. However, the primary focus should be on identifying and treating the underlying cause of the polyclonal gammopathy, rather than the gammopathy itself.
From the Research
Definition and Causes of Polyclonal Gammopathy
- Polyclonal gammopathy refers to an increase in the levels of multiple immunoglobulins (antibodies) in the blood, which can be caused by various conditions such as liver disease, immune dysregulation, or inflammation 2.
- The causes of polyclonal hypergammaglobulinaemia can be divided into eight categories: liver disease, autoimmune disease and vasculitis, infection and inflammation, non-haematological malignancy, haematological disorders, IgG4-related disease, immunodeficiency syndromes, and iatrogenic (from immunoglobulin therapy) 2.
Diagnosis and Management
- Measuring serum concentrations of C-reactive protein and IgG subclasses can be helpful in diagnosing polyclonal hypergammaglobulinaemia 2.
- In most cases, managing polyclonal hypergammaglobulinaemia simply involves treating the underlying condition 2.
- Rarely, polyclonal hypergammaglobulinaemia can lead to hyperviscosity, requiring plasmapheresis 2.
Association with Other Conditions
- Polyclonal gammopathy can be associated with other conditions such as mixed cryoglobulinaemic glomerulonephritis and monoclonal gammopathy of undetermined significance 3.
- It can also be seen in patients with Kaposi's sarcoma, angioimmunoblastic lymphadenopathy, and liver disease due to alpha 1-antitrypsin deficiency 4.
Treatment with Polyclonal IgM-Enriched Immunoglobulins
- The use of polyclonal IgM-enriched immunoglobulins as an adjunct to antimicrobial treatment has been shown to improve outcomes in patients with severe infections by multidrug-resistant Gram-negative bacteria 5.
- A study found that treatment with IgGAM, a polyclonal IgM-enriched immunoglobulin preparation, was associated with a lower 28-day mortality rate and a longer time to breakthrough bacteraemia compared to untreated patients 5.