Heterophile interference accounts for method-specific dsDNA antibodies in patients receiving anti-TNF treatment.

To evaluate analytical explanations for the highly reported incidence of antibodies to dsDNA in patients receiving TNF antagonists. Sixty serum samples from patients receiving biological anti-TNF medication were assessed for the presence of dsDNA antibodies using three standard diagnostic platforms [ELISA, IIF and multiplex bead array (MBA)], before and after treatment to block heterophile antibodies. Results were compared with those obtained using serum samples from patients with SLE. We identified significant method-specific discrepancies in the estimation of dsDNA antibodies in patients receiving TNF antagonists. dsDNA antibodies were frequent according to ELISA and IIF, but rare according to MBA. Blockade of heterophile antibodies resulted in a significant reduction in titres of dsDNA antibodies detected by IIF. In contrast, there was a much greater consistency for dsDNA antibody results in SLE, especially for those present in high titre, and blockade of heterophile antibodies did not result in a change between the two paired samples by IIF or MBA. There is a significant method-specific variation in the detection of dsDNA antibodies in patients receiving TNF antagonists, due in part to the effects of heterophile antibodies.