Intravenous immunoglobulins: can the blood pressure response in laboratory animals be considered a predictive criterion for good clinical tolerance?

Having noted that the only physico-chemical and biological test recommended cannot ensure good tolerance of i.v. IgG in man, we studied a physiological test consisting of evaluating blood pressure during infusion in conscious dogs (10 mg/kg/min) or after i.v. injection in rats (250 mg/kg in 12 sec.). The data were obtained on more than 100 dogs and 500 rats. For preparations known to be well tolerated in man or inducing a few clinical intolerances, the correlation with hypotension in rats and dogs seems good. Therefore, we think this test has its place in the battery of i.v. IgG qualification tests carried out before passage to man. Institut Mérieux has developed a new intact i.v. IgG equilibrated in sub-classes, without PKA, low in IgA and not hypotensive in these two species.

Antibody spectrum and anticomplementary activity of a plasmin-treated human immunoglobulin preparation.

A commercial plasmin-treated human immunoglobulin was studied for its antibody spectrum and anticomplementary activity. Except for a decrease in anti-vaccinia antibody titers in two of three paired samples collected before and after plasmin treatment, there was practically no fall in titers of diphtheria antitoxin and of antibodies to measles, rubella and mumps viruses. Among the three major fractions isolated from the preparation, the plasmin-resistant 7S IgG fraction showed the highest anticomplementary activity when tested by our routine method described in the "Japanese Minimum Requirements'. The Fab fraction showed moderate anticomplementary activity which was thought to be due to the selective consumption of C3. On the contrary, the Fc fraction was not found to be anticomplementary in our test method. In some of the above-mentioned features, the preparation seems to be different from the domestic product formerly studied by ourselves.

Clinical tolerance and catabolism of plasmin-treated gamma-globulin for intravenous application.

Plasmin-treated gamma-globulin of placental origin was tested in clinical and laboratory studies and found to be suitable for intravenous use both for prophylactic and therapeutic purposes. Plasmin treatment of gamma-globulin (IgG) results in proteolytic cleavage of 60-70% of the molecules into Fab and Fc fragments whereas 30-40% of the molecules are plasmin resistant. The antibody spectrum of plasmin-treated gamma-globulin is similar to that of standard gamma-globulin. Catabolic properties of the plasmin-resistant portion of this preparation and of standard gamma-globulin are identical. Plasmin-treated gamma-globulin has no anticomplementary activity and its intravenous administration is well tolerated even by highly sensitive immunodeficient patients.