ESTIMATION OF THE LYTIC CAPACITY OF HUMAN SERUM BY EXPERIMENTAL AND MATHEMATICAL ANALYSIS

Summary. The dynamics of human complement consumption by immune complexes (ICs) was studied. ICs were formed between blood group A and B erythrocytes (solid phase) or synthetic blood group A and B active trisaccharides (fluid phase) respectively, and anti- A/anti-B monoclonal (IgM) blood group antibodies (mAb). We found that the lytic capacity of the human serum was already reduced when the estimated molecular concentration of complement components per erythrocytes were in large excess suggesting that the lytic capacity could be significantly smaller than that one would expect according to the one hit theory of complement-me diated lysis (Mayer M.M., 1961). A new mathematical model of complement consumption was successfully fitted to the entire experimental database containing 4672 measurements. It was used to estimate reactions in undiluted serum containing a physiological erythrocyte concentration, which cannot be measured directly. The model predicted that: (i) up to 40% of all the erythrocytes could be lysed; (ii) the lytic capacity can be significantly reduced by preincubation with 10 to 100 μg/ml ICs. The clinical implications of these findings concerning the reduction of harm caused by unintended transfusion of ABO incompatible blood, and the usefulness of synthetic oligosaccharides to overcome hyperacute rejection (HAR) of xenotransplants are discussed.