Erroneous results with routine laboratory testing for immunoglobulins due to interference from circulating immune complexes in a case of hyperviscosity syndrome associated with autoimmune disease

A patient with the hyperviscosity syndrome exhibited very high concentrations of intermediate to small circulating immune complexes (CIC), involving 40-50% of the IgG present, with IgG rheumatoid factor activity. We demonstrate that precipitation of CIC by polyethylene glycol in the reaction mixture caused interference with nephelometric methods for measuring IgM and IgA, and that failure of immunoglobulins to migrate, owing to molecular interactions, caused interference with radial immunodiffusion methods. Semiquantitative values for immunoglobulins were difficult to interpret on immunoelectrophoresis. As a result, IgM and IgA could only be quantitatively estimated by an end-point nephelometric approach that included a serum blank. Immunoelectrophoresis indicated that a large proportion of the immunoglobulins behaved as aggregates. Immunofixation electrophoresis did not reveal the presence of aggregates. The polyethylene glycol-IgG test provided an accurate assessment of the CIC concentration; the Raji cell and C1q-binding assays did not. Evidently, special techniques may be necessary for accurate determination of immunoglobulin concentrations when CIC concentrations are very high.