Analysis of the Plasma Concentration of Tacrolimus: A Useful Method for Distinguishing Falsely Elevated Tacrolimus Concentrations Reported by the ACMIA

摘要

Tacrolimus monitoring is essential because tacrolimus has a narrow therapeutic dose range. A 35-year-old male after kidney transplantation showed unusually high tacrolimus concentrations in the affinity column mediated immunoassay (ACMIA).Methods: His whole blood tacrolimus concentrations were measured by the ACMIA, microparticle enzyme immunoassay (MEIA), enzyme-linked immunosorbent assay (ELISA) ， and the enzyme multiplied immunoassay technique (EMIT). Since the findings were discrepant, the possible causes were investigated. To screen for endogenous ^-galactosidase, the cyclosporin A concentration of the patient's sample was measured by ACMIA. To determine whether the false increase was attributable to his plasma, tacrolimus concentrations were measured in the whole blood and plasma of the patient in question and 3 other patients. To eliminate heterophilic antibodies, the patient's plasma was treated with heterophilic blocking tube. To eliminate immunoglobulin interference, the patient's plasma was incubated with Protein A or G. Results and Discussion: The patient's tacrolimus concentration was found to be 16.4， 3.7, 3.2, and 3.0mug/L by the ACMIA, MEIA, ELISA, and EMIT, respectively. In the cyclosporin assay, the absorbance did not increase; therefore, beta-galactosidase participation was ruled out. Tacrolimus is mainly sequestered in erythrocytes; however, this patient's plasma and whole blood showed similar tacrolimus levels. Heterophilic blocking tube did not affect the patient's tacrolimus level. His tacrolimus concentration was reduced after incubation with Protein A, indicating that immunoglobulins trapped by Protein A had non-specifically interfered with the assay system.Conclusion: When the tacrolimus level indicated by the ACMIA is unexpectedly high, the patient's plasma should be assayed. If the tacrolimus plasma level is subsequently found to be high, the original result might be incorrect, and it is recommended that another method be used.