[Anti-verotoxin-neutralizing antibody in intravenous gammaglobulin preparations]

Abstract

Intravenously administered immune globulin therapy has been reported to be an effective treatment for serious patients with verotoxin-producing Escherichia coli infections while an efficacy for VT2 are under discussion. We therefore examined in vitro commercially available immune globulin preparations for the presence of anti-VT neutralizing antibodies in expectation of protecting a patient from serious complications as HUS. We examined 47 lots of gamma-globulin prepared by 5 pharmaceutical companies in Japan. Of them 29 lots were prepared from imported blood and 18 lots were from Japanese donors' blood. They were prepared in each company following their own manufactures' process. Neutralizing activity for VT1 and VT2 were determined by means of cytotoxicity using ACHN (renal adenocarcinoma, human) cells. All lots of gamma-globulin preparations from imported blood completely neutralized 125 pg/ml VT1 at the concentration of 12.5 mg/ml, and no significant difference was found in the manufactures' process. On the other hand gamma-globulin preparations from Japanese donors' blood neutralized VT1 five times less than the former. None of all preparations neutralized VT2. Gammaglobulin preparations were produced from pooled human plasma. To know the difference of neutralizing activities in the source, we examined randomly selected 239 human plasma samples of which 51 were from Japanese donors' blood and 188 were from imported blood. Prevalences of neutralizing activity of VT1 in imported plasma and domestic plasma were 10.6% and 2.0%, respectively. The prevalence of neutralizing antibody in these plasma samples reflects the different neutralizing activity of VT1 in gamma-globulin preparations prepared from imported blood and Japanese donors' blood. From these results, by selecting the lot of gamma-globulin preparations or the material of plasma with highly neutralizing activity, intravenously administered immune globulin therapy may be effective for VT1. The lack of VT2-neutralizing activity in any gamma-globulin preparation promotes us to develop humanized anti-VT2-monoclonal antibody for the prevention of HUS in high risk children.