Macroglobulinemia is Characterized by Increased IgM
Macroglobulinemia is characterized by increased monoclonal IgM immunoglobulin. This is the defining feature of Waldenström macroglobulinemia (WM), a distinct B-cell lymphoproliferative disorder.
Diagnostic Features of Waldenström Macroglobulinemia
Waldenström macroglobulinemia is defined by:
- Monoclonal IgM protein in the serum 1
- Bone marrow infiltration with lymphoplasmacytic cells (>10%) 1
- Typical immunophenotype (surface IgM+, CD19+, CD20+) 1
The diagnosis requires both the presence of the IgM monoclonal protein and lymphoplasmacytic infiltration of the bone marrow. This distinguishes it from other monoclonal gammopathies such as IgG or IgA-producing disorders 1.
Clinical Manifestations Related to IgM Overproduction
The increased IgM production in macroglobulinemia leads to several clinical manifestations:
- Hyperviscosity syndrome: Due to the pentameric structure of IgM, which makes it particularly prone to causing serum hyperviscosity 1
- Peripheral neuropathy: Often associated with anti-myelin-associated glycoprotein (anti-MAG) antibodies 1, 2
- Cold agglutinin disease: Frequently associated with IgM-κ monoclonal protein 1
- Cryoglobulinemia: IgM can precipitate at lower temperatures causing symptoms 1
Distinguishing from Other Monoclonal Gammopathies
Unlike multiple myeloma (which typically involves IgG or IgA), Waldenström macroglobulinemia:
- Is specifically characterized by IgM monoclonal protein 1, 3
- Has lymphoplasmacytic morphology rather than plasma cell predominance
- Often involves visceral organs including liver and spleen 1
- Has a distinct genetic profile with MYD88 L265P mutation in >90% of cases 3, 4
Treatment Considerations
Treatment is only initiated when the disease becomes symptomatic. Indications include:
- Symptomatic hyperviscosity
- Anemia with hemoglobin <10 g/dL
- Thrombocytopenia <100 × 10^9/L
- Bulky lymphadenopathy or organomegaly
- Symptomatic neuropathy or cryoglobulinemia 1, 5
First-line treatment typically includes rituximab-based regimens, often in combination with other agents such as bendamustine, cyclophosphamide, or bortezomib 2, 6.
In summary, macroglobulinemia is specifically characterized by increased monoclonal IgM production, distinguishing it from other monoclonal gammopathies that involve different immunoglobulin classes.