Safety tests of the intravenous tolerance of immunoglobulins. Multicenter study of the section 'Blood Plasma Constituents' of the German Association of Transfusion Medicine and Immunohematology (DGTI).

The Working Group 'Blood Plasma Constituents' of the DGTI has carried out four multicenter trials with human immunoglobulins for intravenous application (IVIG). The ACA method elaborated here has led to relatively consistent ACA results for commercially available IVIG preparations in the participating laboratories. On their own, the in vitro tolerance tests of the IVIGs are not sufficient for safety testing, since there is no clear correlation between the ACA values and the tolerance in a rat model in which changes of blood pressure, pulse rate, ECG and respiratory resistance after administration of IVIGs are determined. The role of polymer constituents in tolerance reactions is to be regarded as substantiated, whereas the tolerance of the dimer fractions of beta-propiolactone-treated IVIGs does not differ appreciably from that of their monomer constituents. Determination of the IgG subclass composition requires standardization. The collation of the antibody specificities to the subclasses must be clarified before making inferences with regard to the clinical significance of the subclass composition of the preparations.