Characteristics of Monoclonal Immunoglobulins That Interfere with Serum Inorganic Phosphate Measurement

Abstract
The measurement of inorganic phosphate using an unmodified acid/molybdate assay is known to be subject to interference when paraproteinaemia exists. This phenomenon, due to precipitation in the reaction mixture, is not common to all paraproteins. We studied sera from 35 patients to determine whether interference in the assay was related to particular electrophysical characteristics of the paraproteins. There were spuriously elevated phosphate concentrations in 48·6% of the sera assayed. This could not be related to a direct effect of light chain type, electrical charge or IgG subclass. No IgA paraproteins were found to cause interference but there were immunoglobulin G (IgG) and immunoglobulin M (IgM) paraproteins in both the ‘interfering’ and ‘non-interfering’ groups. The median paraprotein concentration was similar in both groups but, where interference occurred, the degree increased in line with the paraprotein concentration. Although it does not seem possible to predict which samples will cause interference, it is important that the clinical implications of this problem are appreciated.