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1 Laboratoire de Biochimie, Hôpital Edouard Herriot, 5, Place d’Arsonval, Lyon 69437, France
2 Service de Techníques, Nucléaires et Biophysiques, Centre Hospitalier Lyon Sud, Pierre-Bénite 69495, France
aAuthor for correspondence. Fax 33-4-7211-0597.
To the Editor:
We describe a case of a spurious increase in serum thyroid-stimulating hormone (TSH) attributed to a circulating human anti-mouse antibody (HAMA) in a two-site mouse monoclonal antibody-based assay.
A 71-year-old woman on long-term levothyroxine therapy was referred for investigation of uveitis. Her serum TSH had been maintained within the usual reference interval for more than a decade. The initial TSH value by an immunometric method (assay A) on the Dimension RxL analyzer (Dade Behring) was 7.5 mIU/L (reference interval, 0.34–4.82 mIU/L). Because of this unexpected result, it was checked by another method (assay B), a two-site chemiluminescent immunometric assay (Third Generation TSH on the Immulite 2000; DPC Corp.). The TSH value for the same serum was 0.36 mIU/L (reference interval, 0.25–4.60 mIU/L), and free thyroxine was 18.8 pmol/L (reference interval, 10.3–25.5 pmol/L).
In assay A, chromium dioxide particles are coated with mouse monoclonal antibodies specific for the intact TSH, and detection is by an alkaline phosphatase-labeled mouse F(ab')2 fragment specific for the TSH subunit. In assay B, the first mouse monoclonal antibodies specific for TSH are bound to a polystyrene bead, and detection is by an alkaline phosphatase-labeled goat polyclonal antibody preparation.
After addition of a blocking reagent composed of binders to inactivate heterophilic antibodies (HBT; Scantibodies Inc.), serum TSH on the Dimension RxL was 0.49 mIU/L. HAMA (IgG) measured by ELISA (Medac Diagnostika) was 253 µg/L (reference values, <40 µg/L).
In two-site (sandwich) immunoassays, HAMA present in serum can interfere by bridging between the mouse immunoglobulin capture antibody and the mouse immunoglobulin conjugate (1). The use of F(ab')2 fragment eliminates the interference of anti-FC region heterophilic antibodies, but the interference of anti-idiotypic antibodies remains. Interference by HAMA or by an antibody with HAMA activity has been described previously with TSH assays from other manufacturers (2)(3)(4). This is the first description of such interference in TSH measurements on the Dimension RxL. Several authors have proposed the addition of nonspecific animal immunoglobulins from the same species or from other species to prevent binding with HAMAs (5)(6). We understand that assay A has been reformulated with bovine gamma globulins. We retested the sample with the reformulated assay and obtained a value within the reference interval (0.34 mIU/L). We conclude that the presence of heterophilic antibodies should be considered when measured TSH concentrations are not compatible with either the clinical history or other thyroid functions tests.
Footnotes
Editor’s Note: The manufacturer declined to comment.
References
antibody to Escherichia coli produces false-positive results in multiple immunometric assays. Clin Chem 2000;46:1157-1161.The following articles in journals at HighWire Press have cited this article:
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  R. Sapin, A. Agin, and F. Gasser Misleading High Thyrotropin Results Obtained with a Two-Site Immunometric Assay Involving a Chimeric Antibody Clin. Chem., May 1, 2004; 50(5): 946 - 948. [Full Text] [PDF]
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