Intravenous immunoglobulin administration may obscure the detection of small monoclonal proteins in patients with multiple myeloma

Objectives Patients with multiple myeloma (MM) undergoing treatment increasingly receive intravenous immunoglobulin (IVIG) therapy for hypogammaglobulinemia and immunosuppression. Here we sought to investigate whether IVIG administration can obscure small monoclonal (M) proteins on serum protein electrophoresis and immunofixation electrophoresis (IFE) in patients with MM. Methods As a proof of concept, we performed a spiking experiment with increasing concentrations of IVIG added to a patient serum sample containing a small IgG κ restricted band. We also performed a qualitative retrospective review of patient samples and present 2 instructive cases. Serum protein electrophoresis (SPE) was performed using capillary zone electrophoresis, and IFE was conducted using gel electrophoresis to assess the visibility of M-proteins before and after IVIG exposure. Results The spiking experiment demonstrated that IVIG can fully obscure a small band at clinically relevant levels. Clinical observations revealed that while an anodal γ region λ restricted band remained visible, a γ region IgG κ band was completely obscured by the broad, diffuse increase caused by IVIG. Conclusions Administration of IVIG may lead to false-negative SPE/IFE interpretations by masking small monoclonal proteins. Because the detection of M-proteins is critical for distinguishing between complete response and very good partial response or identifying disease relapse, laboratory professionals must be aware of a patient’s IVIG treatment status when interpreting electrophoresis results.