Serum protein electrophoresis pattern associated with elevated polyclonal IgG4 concentrations: a monoclonal-mimicking...

To estimate the frequency and characterize the distinctive features of the serum electrophoretic pattern associated with polyclonal elevations of IgG4, and to evaluate its clinical relevance.

A total of 127,827 serum protein electrophoresis (SPEP) analyses performed in our laboratory over two years were evaluated. Cases exhibiting suggestive morphology, an IgG4 concentration greater than 1.35 g/L, and no monoclonal component (MC) at serum immunofixation electrophoresis (SIFE) were classified as true positives.

We selected 283 electropherograms from 112 individual patients. The characteristic morphological features included a narrow, bell-shaped rise in the anodal gamma globulin region, potentially mimicking an MC, a reduction in the albumin fraction, and an increased beta-2 globulin zone exhibiting a β-γ bridging pattern, without a necessary association with hypergammaglobulinemia and with normal IgA and IgM concentrations. SIFE revealed a pseudoclonal restriction, and the serum free light chain ratio was altered in 29 % of cases, complicating the interpretation of the serum protein profile. The observed frequency was 3 per 1,000 SPEPs. Notably, 59 % of newly identified cases with elevated IgG4 concentrations at our center during the study period were unexpectedly detected by SPEP.

The SPEP pattern associated with elevated polyclonal IgG4 concentrations is significant not only as an MC mimicker to be recognised in the diagnostic workup of plasma cell dyscrasias, but also because, when confirmed by IgG4 measurement, it provides physicians with clinically relevant information, particularly within the context of IgG4-related conditions, potentially preventing unnecessary procedures that could harm the patient and delay diagnosis.