ANAPHYLAKTOIDE REAKTIONEN NACH DEXTRAN. I. IMMUNOLOGISCHE GRUNDLAGEN UND KLINISCHE BEFUNDE

The antidextran dextran system was studied in vitro and in vivo in two animal models and in man with the ultimate aim of preventing dextran-induced anaphylactoid reactions (DIAR). In vitro, a gel diffusion method was developed which permits one to estimate the inhibition of precipitation between dextran and antidextran by monovalent dextran fragments of 3-7 glucose units (hapten inhibition). Using rabbit antidextran antisera for sensitization, a model of heterologous passive antidextran anaphylaxis was developed in guinea pigs. It could be shown that the intensity of anaphylactic shock depended on the amount of sensitizing antibodies, the molecular weight, and the amount of challenging dextran. In this model, a complete inhibition of cytotropic anaphylaxis was achieved by low molecular weight dextran fragments. Thus, the principle of hapten inhibition is also effective in vivo and can be applied as prophylactic measure. A dog model of dextran antidextran anaphylaxis was established by immunization with edestindextran. Circulating dextran reactive antibodies (DRA) could be demonstrated in this model by passive hemagglutination. Anaphylactic reactions corresponding to the type of aggregate anaphylaxis could be elicited by challenge with clinical dextran. The frequency and severity of these reactions could be reduced significantly by pretreatment or admixture of monovalent dextran fragments (hapten dextran). Immunological findings in the dogs made hypersensitive to dextran were similar to those in patients who had experienced DIAR. In the latter, DRA of the IgG-, IgM- and IgA-classes could be demonstrated by passive hemagglutination and red cell-linked antigen antiglobulin reaction (RCLAAR). Patients with severe DIAR showed high titres of circulating DRA. DRA of IgE-class could be demonstrated neither by passive cutaneous anaphylaxis in monkeys nor by radioallergosorbent test. In severe cases of DIAR the complement factor C1(q) was found to be significantly lowered. The differentiation of Ig classes of DRA by RCLAAR showed high titres of IGG, IgM and IgA with predominance of IgG in patients with severe reactions. In individuals with high DRA titres who tolerated dextran infusion, the IgM fraction predominated. These findings permit to classify severe DIAR in humans as immune complex anaphylaxis (aggregate anaphylaxis). Elicitation of DIAR is effected in connection with the infusion of dextran by formation of specific immune complexes with subsequent release of vasoactive mediators. Therefore, specific inhibition of ommune complex formation by preinjection or admixture of monovalent hapten dextran was proposed as a new potential prophylactic measure. Clinical trials of this type have recently been started.