Flushing out the body's IgG antibodies in people with neurological complications after Escherichia coli infection can significantly improve symptoms, according to an Article published by The Lancet. This finding, along with the pattern of neurological complications occurring 1 week after the onset of enteritis, suggests that antibodies against E. coli caused the neurological problems seen in the 2011 outbreak of the bacterium, say the authors.
During the E. coli outbreak in Europe earlier this year, Prof Andreas Greinacher, Institut für Immunologie und Transfusionsmedizin, Universitätsmedizin, Greifswald, Germany, and colleagues suspected the timing of the onset of neurological problems implicated the bodies' own antibodies. The researchers treated 12 patients aged 38-63 years who had severe neurological complications associated with haemolytic uraemic syndrome with a technique called IgG immunoadsorption, which removes the circulating immunoglobulins. To prevent other infection, the patients were infused with intravenous IgG after two rounds of immunoadsorption. All 12 patients survived, and ten had complete neurological and renal function recovery. The team scored the patients neurological impairment, such as hallucinations or aphasia, daily, and immunoadsorption improved this score.
Before immunoadsorption, the patients' symptoms had not responded to plasma exchange and eculizumab (a monoclonal antibody that blocks complement, a component of the immune response).
The findings offer important clues to the mechanisms behind the neurological symptoms. The authors say: "The rapid response that we noted to immunoadsorption makes it unlikely that all neurological symptoms and signs reported were caused by a direct toxic effect of the α subunit of Shiga toxin within the neurons."
They conclude that "immunoadsorption is much more effective in removing antibodies than is therapeutic plasma exchange, which is the treatment most often used for severe microangiopathy-associated organ dysfunction, including severe haemolytic uraemic syndrome."
In a linked Comment, Jon Jin Kim, Evelina Children's Hospital, London, who described the study as a "well thought out prospective cohort trial", said: "Immunoadsorption was reported to be a promising therapeutic option for patients with neurological sequelae, and the outcomes suggest a novel pathophysiology involving IgG in diarrhoea-associated haemolytic uraemic syndrome."
Prof Andreas Greinacher, Ernst-Moritz-Arndt Universität, Institut für Immunologie und Transfusionsmedizin, Klinikum/Sauerbruchstrasse, Greifswald, Germany. T) +49-3838-865482 E) greinach@uni-greifswald.de
Dr Jon Jin Kim, Evelina Children's Hospital, Paediatric Nephrology, London, UK. E) jonjinkim@doctors.org.uk
Journal
The Lancet