Are myeloproliferative disorders associated with decreased immunoglobulin (Ig) levels?

Myeloproliferative Disorders and Immunoglobulin Levels

Myeloproliferative disorders are not typically associated with decreased immunoglobulins; rather, they more commonly demonstrate polyclonal increases in immunoglobulin levels or monoclonal gammopathies, though a minority of patients may show decreased levels.

Pattern of Immunoglobulin Abnormalities in Myeloproliferative Disorders

The immunologic profile in myeloproliferative disorders shows a distinct pattern that differs from primary immunodeficiencies:

Most Common Finding: Polyclonal Increases

• Approximately 32-33% of patients with myelodysplastic syndromes (a related myeloid disorder) demonstrate polyclonal rises in serum immunoglobulins, representing the most frequent immunoglobulin abnormality in these conditions 1, 2.
• This polyclonal hypergammaglobulinemia appears as a broad-based elevation in the gamma region on serum protein electrophoresis, reflecting increased production from multiple plasma cell clones 3.
• The polyclonal increase likely reflects chronic inflammation and immune dysregulation associated with the underlying clonal hematopoiesis 4.

Monoclonal Gammopathies

• Monoclonal gammopathy occurs in approximately 11.5-12.5% of patients with myeloproliferative/myelodysplastic disorders, appearing as discrete peaks on electrophoresis 1, 2.
• These monoclonal proteins must be distinguished from multiple myeloma or MGUS through appropriate clinical correlation and bone marrow examination 3.

Decreased Immunoglobulins: The Minority Pattern

• Only 5.8-19% of patients with myeloproliferative disorders demonstrate decreased immunoglobulin levels, making this the least common immunologic abnormality 1, 2.
• When hypogammaglobulinemia does occur, it represents suppression of normal plasma cell function rather than a primary immunodeficiency 5.

Clinical Implications

Infection Risk

• The 2-fold increased risk of bacterial and viral infections in patients with plasma cell disorders relates primarily to suppression of uninvolved (polyclonal) immunoglobulins when monoclonal gammopathy is present, occurring in approximately 25% of such cases 5.
• Patients with true hypogammaglobulinemia may require closer monitoring for infections, though this represents a minority of cases 1.

Diagnostic Approach When Evaluating Immunoglobulins

• Obtain serum protein electrophoresis (SPEP) to distinguish polyclonal increases from monoclonal peaks 3.
• Perform immunofixation electrophoresis when a discrete peak is identified or clinical suspicion for monoclonal protein remains high 3.
• Quantitative immunoglobulin levels (IgG, IgA, IgM) should be measured to identify specific patterns of elevation or suppression 5.

Distinguishing from Primary Immunodeficiency

• Primary immunodeficiencies typically present with absent or severely reduced B cells and profound hypogammaglobulinemia (often <200 mg/dL total immunoglobulins) 5.
• Myeloproliferative disorders maintain B-cell populations and more commonly show polyclonal increases or normal levels 1, 2.
• The presence of organomegaly, cytopenias, and bone marrow findings of myeloproliferation distinguish these conditions from primary immunodeficiency 4.

Common Pitfalls to Avoid

• Do not assume immunoglobulin abnormalities in myeloproliferative disorders always mean decreased levels—polyclonal increases are actually more common 1, 2.
• Do not overlook monoclonal proteins, which occur in over 10% of cases and require different clinical management considerations 1, 2.
• When hypogammaglobulinemia is present, ensure it is not due to a coexistent lymphoproliferative disorder, which occurred in 8 of 104 patients in one series 1.