Immunoadsorption viable rescue therapy for HUS, neurological deficits

Researchers from Germany report that immunoadsorption is a safe and effective rescue therapy for patients with Escherichia coli O104:H4-induced hemolytic uremic syndrome and accompanying neurological complications, according to recent findings published in The Lancet.

“Our study is the first to show effectiveness of immunoadsorption for treatment of severe neurological complications related to E. coli O104:H4 hemolytic uremic syndrome (HUS),” the researchers wrote. “Immunoadsorption is more effective in removing antibodies than is therapeutic plasma exchange.”

Andreas Greinacher, MD, of the Institute of Immunology and Transfusion Medicine in Greifswald, Germany, and colleagues measured the effect of immunoadsorption as rescue therapy among 12 patients with severe neurological symptoms and recently confirmed E. coli O104:H4.

In June, Greinacher and colleagues treated patients with 12 L plasma volumes of immunoglobulin G immunoadsorption for 2 consecutive days, followed by 0.5 g/kg IV IgG replacement therapy. Composite neurological symptom scores were calculated for each day and changes were assessed before and after immunoadsorption.

All patients survived; 10 patients had complete neurological and renal function recovery; 10 patients required renal replacement therapy by a median of 8 days, and neurological complications occurred at a median of 8 days. Mandated mechanical ventilation occurred in nine patients.

Compared with a neurological symptom score of 3 (P=.038) during the 3 days before immunoadsorption, the neurological symptom score was 1 (P=.0006) 3 days after immunoadsorption.

“As immunoadsorption is a relatively low invasive intervention and intravenous IgG can be used to restore the humoral immune system immediately in case of complications, immunoadsorption should be considered as a treatment in case of severe HUS,” Greinacher told Infectious Disease News.

Greinacher said the antibodies involved need further characterization, and the efficacy of immunoadsorption on neurological outcome and on renal function should be systematically assessed in a prospective, randomized, multicenter trial.

In an accompanying editorial, Jon Jin Kim, MD, of Evelina Children’s Hospital in London, wrote: “Greinacher and colleagues promptly undertook a well thought out prospective, cohort trial in patients with HUS during the recent severe EHEC O104:H4 outbreak. Immunoadsorption was reported to be a promising therapeutic option for patients with neurological sequelae, and the outcomes suggest a novel pathophysiology involving IgG in diarrhea-associated HUS.” – by Ashley DeNyse

For more information:

• Greinacher A. Lancet. 2011;doi:10.1016/S0140-6736(11)61253-1.
• Kim JJ. Lancet. 2011;doi:10.1016/S0140-6736(11)61342-1.

Disclosure: This research was funded by Greifswald University and Hannover Medical School.

Neurologic complications have been reported in cases of HUS caused by Shiga toxin-producing strains of E. coli (STEC). The outbreak of E. coli O104:H4 in northern Germany was associated with a high frequency of HUS, neurologic complications and death in adults. In the study by Greinacher and colleagues, evidence was provided that antibodies produced early in the STEC infection were responsible for the neurologic complications seen. The evidence of antibody mediation of the complications related to the temporal occurrence of neurologic complications starting 1 week after the onset of diarrhea (when antibodies would be expected to start being formed) plus finding that a new procedure of immunoadsorption was clinically beneficial in the disease while plasma exchange and complement-blocking monoclonal antibody treatment clinically failed. The findings may provide insight into the pathogenesis of neurologic disease in HUS caused by strains of STEC and may provide clues into clinically related thrombotic thrombocytopenic purpura. Of perhaps greater immediate importance, the researchers may have found a new treatment for STEC-associated neurologic complications.

– Herbert L. DuPont, MD

Infectious Disease News Editorial Board member

Disclosure: Dr. DuPont reports no relevant financial disclosures.

Follow InfectiousDiseaseNews.com on Twitter.