Study of the immunogenicity and infectivity of hepatitis B-containing stabilized plasma-protein solution.

In early 1984, five patients who were undergoing plasmapheresis at a Melbourne hospital developed a transient hepatitis B surface antigenaemia. A common batch of stabilized plasma-protein solution (SPPS) that was included in the replacement therapy for each patient was found to contain hepatitis B surface antigen (HBsAg). A follow-up study was undertaken of these patients and others who were known to have received SPPS from the same batch (in total, 10 patients were followed for a median of 46.5 weeks). No patient developed evidence of hepatitis, although one patient developed antibody to surface antigen. It was concluded that the manufacturing process was effective in destroying the infectivity of the HBsAg-positive plasma that was used in this batch of SPPS and that the final product was poorly immunogenic in these patients.

Immunoglobulin class and subclass distribution of dextran-reactive antibodies in human reactors and non reactors to clinical dextran.

The red cell-linked antigen-antiglobulin reaction (RCLAAR) with stearoyldextran-coated erythrocytes was used to characterize the immunoglobulin (Ig) classes and IgG subclasses of dextran reactive antibodies (DRA) in 27 dextran reactors (DR) and 96 on reactors (DNR). High titres of dextran reactive IgG were regularly found in sera of patients with severe dextran-induced anaphylactoid/anaphylactic reactions (DIAR) prior to the infusion. In four lethal cases IgG antibodies were found to be in the highest titre range of 16,384 to 32,768. In addition, high IgA and IgM titres were also in severe DIAR. DNR had much lower titres of dextran reactive antibodies of IgG, IgM and IgA classes and IgD antibody was absent in both groups. Dextran reactive IgE antibodies were not demonstrable in DR. Dextran reactive IgG2, IgG3, IgG4 and IgG1 (indirect measurement) were demonstrated in both DR and FNR. Dextran infusion caused variable neutralization in all Ig classes and IgG subclasses, but the contribution of IgG2 was considered most important because of its high titres and most pronounced neutralization in severe DIAR. It is concluded that DRA mainly of the IgG class, play a critical pathogenic role in the induction of severe DIAR, which accordingly is classified as immune complex (Type III) anaphylaxis. The method of RCLAAR allows to delineate a risk group of about 2% of potential reactors.

Pathomechanisms of dextran-induced anaphylactoid/anaphylactic reactions in man.

Immune complex-mediated (type III) anaphylaxis is shown to be the pathomechanism of severe dextran-induced anaphylactic reactions in man. Mild reactions may be either antibody-dependent or not. Patients with severe reactions have regularly high titers of preformed, circulating dextran-reactive antibodies and represent a small subpopulation of high responders to dextran. Upon infusion of clinical dextran, noxious immune complexes are formed, leading to mediator release and symptoms of anaphylaxis. Consequently, application of the hapten inhibition principle is recommended for prevention of such reactions.

[Comparative study on the immunogenicity of plasma substitutes with gelatin base in animal experiments]. / Vergleichende Studie über die Immunogenität von Plasmaersatzlösungen auf Gelatinebasis im Tierexperiment.

The immune response of rabbits and guinea pigs to gelatin and to three commercial plasma substitutes based on gelatin (oxypolygelatin [OPG], di-isocyanate cross-linked gelatin [DCG], modified fluid gelatin [MFG]) has been reevaluated. Passive hemagglutination, passive cutaneous anaphylaxis and active anaphylaxis have been used to detect the response of animals immunized in complete Fruend's adjuvant or in aluminium hydroxide. Marked immune responses were observed with DCG and MFG which were to a large extent specific for the immunizing antigen (i.e. the corresponding chemically modified gelatin). Gelatin and OPG induced weak responses. In contrast to DCG and MFG in systemic anaphylactic shock experiments no anaphylactic shock could be elicited with gelatin and OPG. A limited series of immunizations in guinea pigs of various strains demonstrated that responses to weak immunogens, such as modified gelatins, are markedly influenced by genetic factors.