Alleviation of IgM monoclonal protein interference in nephelometric assays by sample treatment with reducing agent in a chaotropic salt solution.

In some patients, the presence of monoclonal IgM proteins can cause substantial false elevation in nephelometric assays. A 59-year-old woman with previously unrecognized Waldenström macroglobulinemia had high serum viscosity. Nephelometric analysis revealed elevated measured concentrations of IgG, IgA, and IgM. Pretreatment with a reducing salt solution yielded resolution of cross-linked immunoglobulins into a distinct IgM κ monoclonal protein band by immunofixation electrophoresis. Measured quantitative immunoglobulin measurements in treated and untreated specimens were compared. An approximately 50% drop in IgG and IgA concentrations was observed in the presence of reducing agent, while IgM concentrations were unchanged. We report that the addition of reducing agent solution can alleviate artifactual elevation of nephelometric determination of IgG and IgA concentrations. These results are consistent with dissociation of higher order IgM complexes, leading to reduction of nonspecific light scattering by IgM complexes in IgA and IgG nephelometric reactions.