Resolving method-dependent M-protein detection: a case of oligoclonality revealed through complementary immunotyping techniques

OBJECTIVES: This report exemplifies a critical diagnostic pitfall where differing results from two immunotyping methods-immunofixation electrophoresis (IFE) and capillary electrophoresis immunotyping (CE-IT) were the key to identifying an infection-related oligoclonal process, thereby preventing misdiagnosis of a monoclonal gammopathy. DESIGN AND METHODS: We detail the case of a 54 years old febrile woman with active cytomegalovirus infection. Initial diagnostic workup included serum protein electrophoresis (SPE), IFE, and CE-IT. Results were integrated with clinical context, viral serology, serum free light chain analysis, and reviewed multidisciplinary. Confirmatory follow-up studies were performed one month after antiviral therapy. RESULTS: A key finding emerged from comparing the two methods: IFE revealed a faint but discrete, well-defined IgMλ band and a separate, more diffuse λ-band that was not associated with a detectable heavy chain, while CE-IT identified an IgGλ type component. These method-dependent results pointed to an underlying oligoclonal process. The diagnosis of a reactive oligoclonal response was supported by the confirmed viral infection, a normal free light chain ratio, and the absence of other clinical evidence of malignancy. Follow-up confirmed the hypothesis, demonstrating resolution of the initial electrophoretic abnormality and marked attenuation of the IFE band in parallel with clinical and virological improvement. CONCLUSIONS: This case establishes that method-dependent IFE and CE-IT findings should prompt consideration of a reactive oligoclonal etiology. It validates a diagnostic algorithm where such complementary findings, when interpreted within the full clinical context and followed by targeted treatment and short-term monitoring, can definitively resolve the dilemma between benign and malignant paraproteins.