Comparison of thyrotropin-receptor antibodies measured by four commercially available methods with a bioassay that uses Fisher rat thyroid cells

Quantification of thyrotropin-receptor antibodies is important in the diagnosis and management of patients with Graves disease (1). Antibodies with stimulating activity (TSI) have traditionally been detected in bioassays that measure their effect on cloned rat thyroid cells (FRTL-5) or on Chinese hamster ovary (CHO) cells transfected with recombinant human thyrotropin-stimulating hormone (TSH) receptor (2)(3). These assays can detect antibodies in up to 95% of untreated hyperthyroid Graves patients, but, with few exceptions (4), they require cell culture facilities and are labor intensive and time consuming. As an alternative to bioassays, several manufacturers have developed competitive immunoassays that measure the inhibition of the binding of labeled TSH by antibodies in patients’ sera. These methods use porcine TSH receptors and claim clinical sensitivities of ∼90%. They cannot, however, distinguish whether the autoantibodies have blocking or stimulating capabilities, which can be important in a subset of patients. The more recent LUMItest® TRAK (TRAK) human assay (BRAHMS AG) uses human recombinant TSH receptors and luminescence-labeled bovine TSH. The manufacturer’s literature cites a clinical trial that achieved a diagnostic sensitivity of almost 99% with the research version of the DYNOtest® TRAK human assay (5). We have been performing the TSI bioassay with FRTL-5 cells routinely for more than 15 years. The TSI test volumes have increased steadily over that time, requiring an ever-increasing number of assays each week. In 1998, we added the Kronus® TRAb radioreceptor assay (TRAb) to our test menu to reduce the number of requests for TSI. During the preimplementation evaluation of the Kronus reagents, we found equivalent results in 80 of 89 random patient samples. Of the remaining nine samples, five were positive by TSI and not by TRAb, and four were positive by TRAb and not by TSI. The availability of the BRAHMS reagents as well as …