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pISSN 2950-9114 eISSN 2950-9122
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Case Report

J Lab Med Qual Assur 2015; 37(3): 148-152

Published online September 30, 2015


Copyright © Korean Association of External Quality Assessment Service.

False Increase in Whole Blood Tacrolimus Levels due to Interference in an Antibody-Conjugated Magnetic Immunoassay Method

Kyong-Ho Cha, Jeong- Joong Lee, Han-Na Kim, Hyojin Chae, and Yonggoo Kim

Department of Laboratory Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea

Correspondence to:Yonggoo Kim
Department of Laboratory Medicine, Seoul St. Mary’s Hospital, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea
Tel: +82-2-2258-1642
Fax: +82-2-2258-1719
E-mail: yonggoo@catholic.ac.kr

Received: March 25, 2015; Revised: June 14, 2015; Accepted: June 15, 2015

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Tacrolimus is an immunosuppressive agent used to prevent post-transplantation rejection. Tacrolimus has a narrow therapeutic window and therefore, its whole blood concentration is measured for therapeutic drug monitoring. In this report, we present two cases of falsely elevated tacrolimus concentrations identified in recipients of solid organ transplants due to analytical interferences in the antibody-conjugated magnetic immunoassay (ACMIA) method used. Tacrolimus concentrations measured using ACMIA were 4- to 8-fold higher than the values obtained using liquid-chromatography-tandem mass spectrometry (LCMS/ MS) or chemiluminescent micro-particle immunoassay. The cause of this interference remains unknown, but the identification of a possible false elevation of tacrolimus is of paramount importance in clinical practice. Pre-treatment of samples by ethanol extraction or using alternative methods of tacrolimus measurement such as LC-MS/MS are necessary to obtain reliable results in the event of an analytical interference.
(J Lab Med Qual Assur 2015;37:148-152)

Keywords: Tacrolimus, Immunoassay, Interference, Antibody-conjugated magnetic immunoassay

  1. Porayko MK, Gonwa TA, Klintmalm GB, Wiesner RH. Comparing nephrotoxicity of FK 506 and cyclosporine regimens after liver transplantation: preliminary results from US Multicenter trial. U.S. Multicenter Liver Study Group. Transplant Proc 1995;27:1114-6.
  2. Laskow DA, Vincenti F, Neylan J, Mendez R, Matas A. Phase II FK 506 multicenter concentration control study:one-year follow-up. Transplant Proc 1995;27:809-11.
  3. Parikh BA, Siedlecki AM, Scott MG. Specificity of a circulating antibody that interferes with a widely used tacrolimus immunoassay. Ther Drug Monit 2010;32:22831.
  4. Meier-Kriesche HU, Li S, Gruessner RW, Fung JJ, Bustami RT, Barr ML, et al. Immunosuppression: evolution in practice and trends, 1994-2004. Am J Transplant 2006;6(5 Pt 2):1111-31.
    Pubmed CrossRef
  5. Fung JJ, Alessiani M, Abu-Elmagd K, Todo S, Shapiro R, Tzakis A, et al. Adverse effects associated with the use of FK 506. Transplant Proc 1991;23:3105-8.
    Pubmed KoreaMed
  6. Holt DW, Armstrong VW, Griesmacher A, Morris RG, Napoli KL, Shaw LM, et al. International Federation of Clinical Chemistry/International Association of Therapeutic Drug Monitoring and Clinical Toxicology working group on immunosuppressive drug monitoring. Ther Drug Monit 2002;24:59-67.
    Pubmed CrossRef
  7. Wallemacq P, Armstrong VW, Brunet M, Haufroid V, Holt DW, Johnston A, et al. Opportunities to optimize tacrolimus therapy in solid organ transplantation: report of the European consensus conference. Ther Drug Monit 2009;31:139-52.
    Pubmed CrossRef
  8. Rostaing L, Cointault O, Marquet P, Josse AG, Lavit M, Saint-Marcoux F, et al. Falsely elevated whole-blood tacrolimus concentrations in a kidney-transplant patient:potential hazards. Transpl Int 2010;23:227-30.
    Pubmed CrossRef
  9. Wallemacq PE. Therapeutic monitoring of immunosuppressant drugs: where are we? Clin Chem Lab Med 2004;42:1204-11.
    Pubmed CrossRef
  10. Analytical Services International. International proficiency testing scheme: tacrolimus 401 results. http://www.bioanalytics.co.uk/Tacrolimus%20Front%20Pages/tacro239.pdf (Accessed April 10, 2015).
  11. Jeong TD, Gu GG, Chun S, Kim JH; Therapeutic Drug Monitoring Subcommittee, The Korean Association of Quality Assurance for Clinical Laboratory. Annual report on the external quality assessment of therapeutic drug monitoring and testing for drugs of abuse in Korea (2013). J Lab Med Qual Assur 2014;36:12-22.
  12. Chung JW, An D, Song J, Chung HJ, Park HI, Lee W, et al. Performance evaluation of affinity column mediated immunometric assay for tacrolimus. Korean J Lab Med 2009;29:415-22.
    Pubmed CrossRef
  13. Altinier S, Varagnolo M, Zaninotto M, Boccagni P, Plebani M. Heterophilic antibody interference in a nonendogenous molecule assay: an apparent elevation in the tacrolimus concentration. Clin Chim Acta 2009;402:193-5.
    Pubmed CrossRef
  14. Barau C, Frangie C, Goujard C, Tribut O, Parant F, Taburet AM, et al. Falsely elevated whole blood tacrolimus concentrations due to interference in an affinity columnmediated immunoassay method on Xpand dimension. Ther Drug Monit 2009;31:267-8.
    Pubmed CrossRef
  15. Abei M, Yagi M, Watanabe T, Sugimoto K, Tanno Y, Kaito K. Nonspecific reacting materials that interferes tacrolimus assay by ACMIA. Rinsho Byori 2013;61:983-8.
  16. Taguchi K, Ohmura T, Ohya Y, Horio M, Furukawa K, Jono H, et al. False tacrolimus concentrations measured by antibody-conjugated magnetic immunoassay in liver transplant patient: 2 case reports and literature review. Exp Clin Transplant 2014;12:474-8.
  17. Moscato D, Nonnato A, Adamo R, Vancheri M, Caropreso A. Therapeutic monitoring of tacrolimus: aberrant results by an immunoassay with automated pretreatment. Clin Chim Acta 2010;411:77-80.
    Pubmed CrossRef
  18. Yamaoka M, Kawamura R, Shioda Y, Ogawa N, Koyama I, Saitoh T, et al. Analysis of the plasma concentration of tacrolimus: a useful method for distinguishing falsely elevated tacrolimus concentrations reported by the ACMIA. Rinsho Byori 2010;58:1188-92.
  19. Toraishi T, Takeuchi H, Nakamura Y, Konno O, Yokoyama T, Iwamoto H, et al. Falsely abnormally elevated blood trough concentration of tacrolimus measured by antibody-conjugated magnetic immunoassay in a renal transplant recipient: a case report. Transplant Proc 2012;44:134-6.
    Pubmed CrossRef
  20. Siemens Healthcare Diagnostics. Global product support procedures manual: procedure for troubleshooting TACR NSB samples: GLSLS-F-007-1 DCM Rev. 6.0 Effective. Deerfield (IL): Siemens Healthcare Diagnostics, 2008.

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