Heterophilic antibody interference in serum TSH immunoassays can result in misdiagnosis of patients with suspected thyroid disease. Rheumatoid factor (RhF) is an immunoglobulin with reactivity to the Fc portion of human IgG. Some RhF species also cross-react with animal immunoglobulins so have the potential to act as heterophile antibodies. As part of the Cambridge Supra-Regional Assay service for thyroid function testing five serum samples with strongly positive RhF and positive interference in the Siemens Centaur TSH-2 assay (CentTSH-2) were identified. In each case TSH was >20 mU/L, but values dropped into the reference range when diluted 5-fold. TSH was within the reference interval using the Centaur TSH-3 or the Perkin Elmer Auto DELFIA assays. Serum from one patient with a CentTSH-2 of 29.3 mU/L was re-assayed using the DELFIA, Beckman, Roche and Abbott TSH assays with values within the reference range throughout (2.6, 2.4, 1.7, 3.4 mIU/L respectively). To determine whether RhF interference is a universal problem with the CentTSH-2 assay, 4213 patients with concurrent CentTSH-2 and RhF results (Siemens BNII) were identified from the laboratory database. There was no correlation between RhF and TSH values (P=0.81), and no tendency towards high TSH values in RhF-positive patients (P=0.42 for RhF-positive versus RhF-negative patients, t-test). Only a minority of RhF antibodies appear to interfere with the CentTSH-2 assay, and these are likely to be a subclass with cross-species reactivity. It is not clear whether this subclass of heterophilic RhF is different to other RhF antibodies with respect to clinical correlation with rheumatoid arthritis. The positive predictive value of RhF for rheumatoid arthritis is known to be low (~30%), which may be a consequence of this heterogeneity. The Centaur TSH-3 assay appears less susceptible than the CentTSH-2 assay to heterophilic interference, and we would recommend using the newer assay formulation.
Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.