First Steps toward Harmonization of LC-MS/MS Thyroglobulin Assays

[摘要] To the Editor:Antithyroglobulin autoantibodies (TgAbs)1 frequently cause falsely low measurements of serum thyroglobulin (Tg) when immunometric assays (TgIAs) are used (1). This problem can be overcome by tryptic digestion of patient serum with subsequent measurement of Tg-proteotypic peptides by LC-MS/MS (TgMS) (2–4). However, it remains uncertain how different TgMS assays compare with each other, a crucial question in today's laboratory testing environment, wherein concern has been raised over patient samples being tested by different methods or in different laboratories over time (5). We therefore performed a pilot study to assess the intermethod concordance between 4 independently developed TgMS methods. The study was approved by the Mayo Clinic institutional review board.We tested 40 patient serum samples spanning Tg concentrations from <0.1 to 10 ng/mL (assigned by DxI TgIA, Beckman Coulter). We classified the samples as TgAb positive (n = 22) or TgAb negative (n = 18) on the basis of whether they contained TgAb concentrations that exceeded the functional sensitivity of the DxI TgAB assays (1.8 IU/mL). Samples were deidentified and shared between 4 laboratories for TgMS testing: ARUP Laboratories, Laboratory Corporation of America Holdings (LabCorp), Mayo Clinic, and the University of Washington (UWash). Each assay uses different sample preparation methodologies: ARUP and Mayo use different protein precipitation steps to enrich for thyroglobulin before proteolysis, and LabCorp and UWash digest serum samples directly after different denaturing steps. …

[学科分类] 过敏症与临床免疫学