From the Guidelines
Elevated beta 2 microglobulin (β2M) and Immunoglobulin A (IgA) on Serum Protein Electrophoresis (SPEP) are most commonly associated with multiple myeloma, particularly IgA myeloma, and other plasma cell disorders, as well as chronic kidney disease, according to the most recent and highest quality study 1.
Conditions Associated with Elevated β2M and IgA
The following conditions are associated with elevated β2M and IgA:
- Multiple myeloma, particularly IgA myeloma
- Chronic kidney disease
- Chronic inflammatory diseases
- Certain lymphomas, especially mucosa-associated lymphoid tissue lymphomas
- HIV infection
- Autoimmune disorders like rheumatoid arthritis and Sjögren's syndrome
Prognostic Implications
β2M serves as an important prognostic marker in IgA myeloma, with levels above 3.5 mg/L indicating poorer outcomes 1.
Further Testing
When β2M and IgA are elevated, further testing is typically warranted, including:
- Bone marrow biopsy
- Skeletal survey or advanced imaging
- Additional laboratory tests like serum free light chains and immunofixation to confirm the diagnosis and determine appropriate treatment 1.
From the Research
Conditions Associated with Elevated Beta 2 Microglobulin and IgA
- Multiple myeloma: a clonal process that is malignant or potentially malignant, often associated with elevated beta 2 microglobulin (β2M) and Immunoglobulin A (IgA) in a Serum Protein Electrophoresis (SPEP) 2, 3
- Monoclonal gammopathies: conditions characterized by the presence of a monoclonal protein (M protein) in the blood, which can be associated with elevated β2M and IgA 2, 3
- Reactive or inflammatory processes: polyclonal gammopathies may be caused by any reactive or inflammatory process, which can lead to elevated IgA levels 2
- High-risk multiple myeloma: defined by gene expression profiling high risk, t(14;16), t(14;20), del(17p), or amp1q21, primary plasma cell leukemia, and elevated serum lactate dehydrogenase, which may be associated with elevated β2M and IgA 4, 5
SPEP Findings
- A homogeneous spike-like peak in a focal region of the gamma-globulin zone indicates a monoclonal gammopathy, which can be associated with elevated β2M and IgA 2
- Separate β1 and β2 measurements can help identify β-migrating M-proteins, including IgA, which can be elevated in certain conditions 3
Clinical Implications
- Elevated β2M and IgA in a SPEP can be indicative of underlying conditions such as multiple myeloma or monoclonal gammopathies, and require further evaluation and management 2, 3
- The use of bortezomib, lenalidomide, and dexamethasone (RVd) as a treatment regimen for multiple myeloma may be associated with an increased risk of bacterial infections, particularly in patients with high-risk cytogenetics or other underlying health conditions 6