DIFFERENCES IN VEROTOXIN NEUTRALIZING ACTIVITY OF THERAPEUTIC IMMUNOGLOBULINS AND SERA FROM HEALTHY CONTROLS

Intestinal infection by Escherichia coli 0157 and other verotoxin (VT) producing E. coli has been increasingly recognized as an important fa ctor for the causation of classic (enteropathic) hemolytic uremic synd rome (HUS) and hemorrhagic colitis (HC). Toxins most frequently involv ed are VT1 and VT2. As with other toxin-mediated diseases, administrat ion of immunoglobulin (Ig) may be beneficial. However, little is known about the immune response elicited by the toxin(s), and the prevalenc e of VT neutralizing antibodies in the healthy population. We studied the capacity of seven Igs and a commercial plasma preparation to neutr alize four different VTs (VT1, VT2, VT2c and VT2e). The results were c ompared with the neutralization titers (NT50%) of normal human serum s amples from various age groups. Plasma products and normal sera were s eparated by protein G affinity chromatography to investigate the facto r(s) responsible for VT neutralization. All Igs neutralized VT1 (8 to 96 NT50%). None of them inhibited VT2, VT2c or VT2e effectively. In co ntrast, none of 40 pediatric, and only one of 20 adult control sera (s tarting dilution 1 : 4) neutralized VT1 (25 NT50%). All 60 samples as well as the plasma preparation blocked VT2 (22 to 446 NT50%, median 13 7), but not VT2c and VT2e. The VT1 neutralizing activity was eluted wi th the IgG fraction. The VT2 neutralizing activity was not bound by pr otein G, but was recovered in the IgG-free effluent. In conclusion, th erapeutic Igs significantly neutralize VT1, but are largely ineffectiv e against other VTs. In contrast, all control sera inhibited VT2, but rarely VT1. Different principles, notably IgG and non-IgG (probably no n-immunoglobulin) factors, respectively, appear to be responsible for the reduction of VT1 and VT2 cytotoxicity in vitro. Patients with VTEC disease are rarely expected to benefit from the use of presently avai lable Igs.