Human anti-murine antibodies interfere with CPR assays performed with commercial kits

Quantitation of C-peptide is important for the assessment of insulin secret ion, in particular in patients receiving insulin therapy. Since the CPR lev els become much higher than the concentration of C-peptide for several reas ons, such as the high concentration of proinsulin, CPR values sometimes nee d to be assessed carefully. We have had two diabetic patients whose CPR val ues were abnormally high when determined with a Daiichi C-peptide kit III(m ethod 1). CPR values determined by other methods were from two to ten times lower, indicating considerable interference when method 1 was used. Since method 1 uses mouse monoclonal antibodies (mmab) for detection antibodies, we suspected that human anti-murine antibodies (HAMA) were responsible for the interference. HAMA were detected in serum from both patients (45 and 46 0 ng/ml in case 1 and case 2 (at peak), respectively). Removal of HAMA from serum eliminated the interference. Modification of method 1 to exclude mma b from the assay system removed all interference, HAMA were, therefore, con sidered to be the cause of the interference. In case 2, the peak concentrat ion of HAMA was recorded 16 months earlier than the maximum of interference . Further analysis revealed that HAMA with high affinities were responsible for the interference. (C) 2000 Elsevier Science Ireland Ltd. All rights re served.