What is the clinical significance of elevated Immunoglobulin M (IgM) levels?

From the Guidelines

Elevated Immunoglobulin M (IgM) levels are clinically significant as they can indicate the presence of Waldenström's macroglobulinemia (WM), a type of lymphoplasmacytic lymphoma.

Key Points

• Elevated IgM levels can fluctuate independently of tumor cell killing, particularly with newer biologically targeted agents such as rituximab, bortezomib, and everolimus 1.
• A serum IgM level > 60 g/L is associated with an imminent risk of symptomatic hyperviscosity and is considered a treatment indication 1.
• The International Prognostic Staging System for Waldenström’s Macroglobulinemia (IPSSWM) defines 3 risk groups with 5-year survival rates of 87%, 68%, and 36% based on 5 adverse features, including age, hemoglobin, platelet count, β2-microglobulin, and serum monoclonal protein concentration 1.
• Treatment initiation is appropriate for patients with constitutional symptoms, progressive lymphadenopathy or splenomegaly, anemia, or certain complications such as hyperviscosity syndrome or symptomatic sensorimotor peripheral neuropathy 1.
• Response categories for WM include complete response, very good partial response, partial response, minor response, stable disease, and progressive disease, based on serum IgM levels and clinical findings 1.
• A bone marrow biopsy should be considered when serum IgM levels appear out of context with the clinical progress of the patient to clarify the underlying disease burden 1.

From the Research

Clinical Significance of Elevated IgM Levels

Elevated Immunoglobulin M (IgM) levels can be associated with various clinical conditions, including:

• Autoimmune diseases, such as autoimmune hemolytic anemia, cryoglobulinemia, primary biliary cirrhosis, and multiple sclerosis 2
• Primary and secondary hyper-IgM syndromes, which are characterized by defects in immunoglobulin class switch recombination (CSR) 3
• Monoclonal gammopathy, including monoclonal gammopathy of undetermined significance (MGUS), Waldenstrom macroglobulinemia (WM), and B cell non-Hodgkin's lymphoma 4
• Infections, although IgM tests can also suffer from false-positive results, leading to misdiagnoses and inappropriate therapy 5

Diagnostic and Prognostic Implications

Elevated IgM levels can be used as a diagnostic tool, but should be interpreted with caution and in conjunction with other test methods and clinical findings. For example:

• Levels of serum IgM >15.5g/L were found to be 80.6% sensitive and 89.2% specific for the diagnosis of WM 4
• The type of light chain (kappa or lambda) can also be used to help with differential diagnosis 4
• Elevated IgM levels have been associated with an increased risk of total and cause-specific mortality, including mortality due to infectious disease 6

Associated Conditions and Complications

Elevated IgM levels can be associated with various complications and comorbidities, including:

• Autoimmune diseases, such as rheumatoid arthritis and lupus 2
• Infections, such as pneumonia and sepsis 5
• Malignancies, such as lymphoma and multiple myeloma 4
• Neurological disorders, such as neuropathy and POEMS syndrome 4, 3