[Significance of immune complexes in children with severe hemophilia A in substitution treatment with factor VIII concentrates]. / Bedeutung von Immunkomplexen bei Kindern mit schwerer Hämophilie A unter Substitutionsbehandlung mit Faktor VIII-Konzentration.

Sera and EDTA-Plasma of patients with severe Haemophilia A were analysed for immune complexes and the hemolytic activity of complement in relation to Factor VIII replacement, in order to confirm or possibly exclude a relationship to allergic reactions. Immune complexes were isolated by PEG precipitation and quantitated. In addition a solid phase ELISA assay was used to detect complement-binding complexes. Total hemolytic complement activity of the classical and the alternate pathway was measured in addition to the C3 splitproduct C3d. The results obtained from 12 patients with severe Haemophilia A showed slightly increased immune complex titers, no changes of the immune complex levels during Factor VIII replacement and no alteration of the complement system following the infusions. One patient developed an allergic reaction without evidence of complement activation.

Anaphylaxis to L-asparaginase during treatment for acute lymphoblastic leukemia in children--evidence of a complement-mediated mechanism.

L-Asparaginase (l-Asp) is widely used as an effective drug against childhood and adult acute lymphoblastic leukemia (ALL). However, it is immunogenic in humans and may lead to hypersensitivity reactions. The immunological basis of these reactions is not clear. Since the presence of l-Asp specific IgG-antibodies seems to correlate better with clinical reactions than IgE-antibodies and IgG-antibodies are known to be able to fix and activate the complement system, we speculated that the mechanism of anaphylaxis may be complement- rather than IgE-mediated. We analyzed 24 children with ALL (age 2-15 yr) for changes in the complement system during l-Asp infusions. Chemotherapy was administered according to the CoALL 82 protocol which is derived from the CoALL 80 protocol recently published. The formation of specific antibodies of IgM and IgG classes against l-Asp was monitored by a solid phase ELISA. The immunological responsiveness of individual patients varied over a wide range but both types of antibodies were induced. Anaphylactic reactions were observed on eight occasions in eight children. The infusions in the remaining 16 patients were tolerated without clinical reactions. Significant activation of complement was demonstrated in seven of eight reaction occasions and in none of the occasions without reactions. The most important complement activation parameter monitored was the C3 split product C3d measured in EDTA-plasma. We conclude that anaphylaxis to l-Asp in patients with ALL can be explained in most instances on the basis of complement activation induced by the formation of immune complexes of l-Asp and specific antibodies of IgM and IgG classes.