Usefulness of a Thyroglobulin Liquid Chromatography-Tandem Mass Spectrometry Assay for Evaluation of Suspected Heterophile Interference
Recent studies have found the accuracy of human serum thyroglobulin (Tg) measurement by immunoassays can be affected by anti-Tg autoantibodies (TgAB). After reading these studies, Mayo Clinic representatives Brian Netzel, Stefan Grebe, M.D., Ph.D., and Alicia Algeciras-Schimnich, Ph.D. authored the article, "Usefulness of a Thyroglobulin Liquid Chromatography–Tandem Mass Spectrometry Assay for Evaluation of Suspected Heterophile Interference," in the July issue of Clinical Chemistry to describe a methodology implemented in their laboratory which resulted in similar findings.
Netzel, Dr. Grebe, and Dr. Algeciras-Schimnich applied their study methodology to heterophilic antibodies (HAB), which may result in false-high Tg measurements in immunometric assays. The goal of the study was to determine whether Tg measurement by LC-MS/MS would allow accurate quantification in samples with suspected HAB interference.
Their laboratory received requests for investigation of potential HAB interference in the Tg immunoassay (Access, Beckman Coulter) results for seven patients. Each sample was also assayed for Tg using LC-MS/MS. Results of the Access Tg and LC-MS/MS Tg matched for the four samples with negative HAB workup. The other three, likely HAB-positive samples, had serum Tg concentrations below the LOQ (<0.5 μg/L) by LC-MS/MS, but measured as high as 604 μg/L on the Access.
The study concluded that the determination of Tg concentrations by LC-MS/MS obviates the need for extensive HAB workup by classical methods, while providing accurate quantification of Tg in the presence of substantial HAB interferences. Netzel, Dr. Grebe, and Dr. Algeciras-Schimnich propose adopting this approach for all cases of suspected HAB interference in Tg measurement, and hypothesize that this approach could be extended to other analytical targets that can be measured by LC-MS.