Interference of IgM rheumatoid factor with nephelometric C-reactive protein determinations

Different nephelometric assay systems for quantitation of C-reactive protein (CRP) were compared with radial immunodiffusion (RID) and tested for their susceptibility to interference by serum IgM rheumatoid factor (RF). In 3 nephelometric assays, RF was found to elevate CRP values. Sera with high RF content from patients with rheumatoid arthritis gave significantly higher CRP values by nephelometric assay than by RID; the addition of purified RF to RF-negative sera increased CRP values markedly; and removal of RF from sera corrected falsely elevated CRP values. This interference by RF is explained by the action of human RF as a (secondary) antibody reacting with complexed mammalian IgG anti-human CRP in the assay. In this way the nephelometric signal is enhanced to give falsely elevated CRP values. In contrast, the gel diffusion RID method does not suffer from this non-specific interference.