DOI: 10.1097/TP.0b013e31819575a1

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PMID: 19202453

Issn Print: 0041-1337

Publication Date: 2009/02/15


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Human Anti-Mouse Antibodies Interferences in Elecsys PTH Assay After OKT3 Treatment

Etienne Cavalier; Agnès Carlisi; Jean-Paul Chapelle; Paul Orfanos; Marc Uzan; Véronique Falque; Pierre Delanaye; Mourad Hachicha

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Excerpt

We report the case of a 61-year-old white man with end-stage renal disease secondary to an autosomal dominant polycystic kidney disease. Dialysis therapy was commenced in 2003, and he received a renal transplant from a deceased donor in 2004. His circulating parathormone (PTH) concentration before transplantation was 287 pg/mL as measured by the Roche Elecsys immunoassay analyser (Mannheim, Germany), in the target of the K/DOQI recommendations (1). The transplanted kidney functioned until 2007, and then failed because of acute cellular rejection (type II B according to Banff classification). He received standard antirejection medication (intravenously steroids and OKT3) but did not respond, lost function of his renal graft and returned to hemodialysis in February 2007. Four months later, the renal graft was removed because of systemic manifestations of rejection. From March to December 2007, plasma PTH concentrations were measured every 3 months again by Roche Elecsys. The results showed a rise of PTH after 7 months on hemodialysis, and this was even more dramatic after 10 months (Table 1). No parathyroid mass was identified by 99Tc-Sestamibi or ultrasound scans. An interference in the PTH assay was thus suspected, and the sample was sent to the reference laboratory where extra-investigations were performed, as already published (2). The treatment of the sample with heterophilic blocking tubes (Scantibodies, Shantee, CA), which removes human anti-animal antibodies, resulted in an important decrease of PTH, from 3748 to 552 pg/mL. Treatment with antirheumatoid factor (IBL, Hamburg, Germany) did not result in a significant change in PTH. PTH was then measured by a different second-generation chemiluminescent immunoassay (Liaison, Diasorin, Saluggia, Italy) that uses polyclonal anti-goat antibodies, one directed against the N-terminal (aa 1–34) region, and the other one directed against the C-terminal (aa 39–84) part, which showed a result at 605 pg/mL, not altered by inclusion of human anti-animal antibodies or rheumatoid factor (RF). By contrast the suspect Roche Elecys intact PTH assay uses two murine monoclonal antibodies each of which bind to different epitopes on the PTH molecule; the N- terminal (aa 26–32) portion (3), and the C-terminal fragment (aa 38–84). Thus these two assays use antibodies derived from different animal species which bind to different epitopes on the PTH molecule. This led us to conclude that there was an analytical interference in the PTH determination by Elecsys, and that this interference was because of a human anti-mouse IgM.
Treatment with OKT3, a murine monoclonal antibody directed against the CD23 of human T-cell antibodies, is well known to induce the production of human anti-mouse antibodies (4). These antibodies can reduce the efficiency of the drug by blocking the interaction with the target cells, but can also interfere with the immunoassays that use murine antibodies (5). Such interferences are not always obvious to detect, particularly in the case of hemodialyzed or transplanted patients, where high circulating concentrations of PTH can be expected.
In conclusion, physicians should always keep in mind that OKT3 treatment can result in the production of human anti-mouse antibodies. These antibodies can interfere with any immunoassay and give spurious results, leading to unnecessary cost-effective extra-investigations.
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