https://orcid.org/0000-0002-3163-8897
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Jing Cao, Commentary on Hiding in Plain Sight: Protein Electrophoresis Profile Inconsistent with Patient’s Diagnosis, Clinical Chemistry, Volume 71, Issue 2, February 2025, Page 252, https://doi.org/10.1093/clinchem/hvae161
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This report describes inconsistent laboratory findings in a case of Waldenström macroglobulinemia (WM), including the absence of an M component spike in capillary zone electrophoresis (CZE), while immunofixation electrophoresis (IFE) found a monoclonal IgM λ gammopathy. It underscores the complexity of detecting WM when screening for monoclonal gammopathy (MG) due to the atypical symptoms of disease presentation, and the challenge from interference of serum protein electrophoresis.
The issue of IgM multimers potentially affecting electrophoresis results is well documented, as seen with traditional agarose gel electrophoresis (AGE). However, this case demonstrates that even CZE, which is often considered more sensitive for monoclonal protein detection, may yield normal-appearing results due to the presence of IgM multimers.
This highlights the advantages of utilizing multiple analytical tools in MG screening. Advanced testing such as IFE can be performed when abnormalities are seen in AGE or CZE, which may include not only the presence of M component spike but also the delay, mergence, and distortion of α1, α2, β1, β2, and γ regions. Always overlaying the patient’s electrophoretic graph with the reference profile for abnormality evaluation is a particularly powerful analyzing technique. The laboratory's practice of treating specimens with β-mercaptoethanol (β-ME) and performing IFE proved pivotal in uncovering the hidden IgM MG. This emphasizes the value of AGE or CZE review with specific instructions to reflex to IFE when an abnormal electrophoretic pattern is evident and treatment of samples with β-ME when the profile appears delayed or distorted.
