From the Guidelines
Elevated Immunoglobulin A (IgA) levels are a significant indicator of an abnormal immune response that requires thorough medical evaluation, as they can be associated with various conditions such as IgA monoclonal gammopathy, multiple myeloma, chronic infections, autoimmune disorders, liver diseases, or inflammatory bowel diseases. IgA is an antibody that plays a crucial role in protecting mucosal surfaces like the respiratory and gastrointestinal tracts from pathogens. When IgA levels rise above the normal range (typically 70-400 mg/dL in adults), this suggests several possible conditions, and the significance varies depending on the degree of elevation and associated symptoms 1. Mild elevations might reflect a normal response to recent infections, while substantial increases often indicate more serious underlying conditions.
Possible Conditions Associated with Elevated IgA
- IgA monoclonal gammopathy
- Multiple myeloma
- Chronic infections
- Autoimmune disorders (like rheumatoid arthritis or lupus)
- Liver diseases (particularly alcoholic cirrhosis)
- Inflammatory bowel diseases
Evaluation and Management
No specific medication directly treats elevated IgA; instead, treatment targets the underlying cause. Patients with elevated IgA should undergo comprehensive evaluation including complete blood count, comprehensive metabolic panel, and possibly bone marrow examination if myeloma is suspected 1. The immune system produces increased IgA in response to specific triggers, and identifying this trigger is essential for proper management and treatment of the underlying condition. According to the most recent guidelines, a quantitative serum IgA level should be obtained at the time of celiac disease screening 1, and individuals with confirmed elevated IgA levels should be referred to a gastroenterologist for consultation and may require a small-bowel biopsy 1.
Key Considerations
- Elevated IgA levels can be associated with celiac disease, and screening for celiac disease should include testing for IgA autoantibodies to tissue transglutaminase (tTG) 1.
- IgA deficiency can lead to falsely low levels of IgA tTG or EMA assay, and therefore, a quantitative serum IgA level should be obtained at the time of celiac disease screening 1.
- The presence of elevated IgG levels, especially in the absence of cirrhosis, is a distinctive feature of autoimmune hepatitis, and a selectively elevated IgG in the absence of IgA and IgM elevation is particularly suggestive of AIH 1.
From the Research
Significance of Elevated IgA
Elevated Immunoglobulin A (IgA) levels can be significant in various medical conditions. The following points highlight the importance of IgA in different diseases:
- Elevated IgA levels are associated with IgA nephropathy, a common glomerulonephritis worldwide 2.
- IgA deficiency is linked to autoimmunity, particularly celiac disease, and elevated B-lymphocyte stimulator and APRIL serum levels characterize several autoimmune diseases 3.
- In Alcoholic Liver Disease (ALD), IgA levels increase in all stages, and the IgA/IgG ratio correlates with the advancing stages of ALD and the amount of alcohol consumed 4.
- High serum IgA levels in patients with IgG4-related disease are associated with mild inflammation, sufficient disease-specific features, and favorable responses to treatments 5.
- Galactose-deficient IgA1 levels are elevated and heritable in African American patients with IgA nephropathy, indicating a risk factor for the disease 6.
Conditions Associated with Elevated IgA
The following conditions are associated with elevated IgA levels:
- IgA nephropathy 2
- Celiac disease 2, 3
- Alcoholic Liver Disease (ALD) 4
- IgG4-related disease 5
- Autoimmune diseases 3
Clinical Implications
Elevated IgA levels can have significant clinical implications, including:
- Diagnosis and monitoring of IgA nephropathy 2
- Identification of celiac disease in patients with IgA deficiency 3
- Assessment of disease severity and progression in ALD 4
- Prediction of treatment response in IgG4-related disease 5
- Identification of heritable risk factors for IgA nephropathy in African Americans 6