Mercury exposure in protein A immunoadsorption

Abstract

Background. Immunoadsorption is increasingly used to treat antibody-mediated autoimmune diseases. To prevent microbial growth during storage, reusable protein A-Sepharose gel columns are primed with ethyl mercury thiosalicylate (thiomersal, 0.1% solution) and rinsed with phosphate buffer before use. In this study, we tested the hypothesis of systemic mercury exposure in protein A immunoadsorption. Methods. Whole blood mercury levels were measured by atomic absorption spectroscopy before and after protein A immunoadsorption (11 patients, 26 treatments), anti-IgG immunoadsorption (eight patients, 13 treatments) and LDL apheresis (DALI and Therasorb systems; nine patients, 14 treatments). Results. Patients treated with protein A immunoadsorption had significantly elevated baseline mercury levels compared with the other groups, which were not different from healthy controls. Following protein A immunoadsorption, mercury levels increased from 5.9 ± 1.4 μg/l (mean ± SEM, normal, < 5 μg/l) to 32.3 ± 5.7 μg/l, P < 0.001). In one intensively treated patient, acute neurological toxicity developed at a mercury level of 107 μg/l. Symptoms abated slowly and did not recur after switching to a thiomersal-free system and chelation therapy. No mercury release to patients occurred in anti-IgG immunoadsorption or LDL apheresis treatments. Conclusion. This preliminary report suggests that protein A immunoadsorption columns primed with thiomersal during storage may cause a sustained increase of systemic mercury concentrations, which exceed current safety recommendations in a proportion of patients. Considering the potential for mercury-induced toxicity, every effort should be undertaken to reduce systemic mercury exposure, either by adding chelators to the rinsing solution or ideally by replacement of thiomersal.