A 16‐yr‐old girl with severe von Willebrand disease complicated by the development of precipitating alloantibodies to von Willebrand factor (anti‐VWF) had a life‐threatening anaphylactoid reaction immediately after the infusion of a commercial plasma concentrate of factor VIII/von Willebrand factor. An early post‐infusion activation of the complement system was demonstrated by the appearance of C3 split products and by the drop of serum CH50 activity, occurring in parallel with a post‐infusion drop in the anti‐VWF antibody levels. Immune complexes remained unchanged in the early post‐infusion period and rose to a moderate extent only after 24 h. We conclude that biologically active products of the complement system contributed to the onset of this life‐threatening reaction which occurred after concentrate infusion.
Complement-fixing antibodies to trophoblast represent a better marker to discriminate patients with recurrent spontaneous abortions from controls and are cytotoxic for the target cells. Anti-endothelial antibodies are also present in these patients and exhibit pro-inflammatory and pro-coagulant activities.
The susceptibility of trophoblast to cytolysis by human complement was investigated using cells purified to over 90% from first trimester placentae. Two assay systems were employed to measure the killing of trophoblasts, an antibody-dependent complement-mediated cytolysis and the reactive lysis. The antibody obtained from a patient with Addison's disease reacted specifically with syncytiotrophoblasts and induced a dose-dependent killing of the cells not exceeding 50% even in the presence of excess antibody and complement. The percentage of cells killed by the terminal complement complex in the reactive lysis system was somewhat higher, reaching values of 60%. Immunofluorescence analysis revealed the presence of CD46 and CD59 on all syncytiotrophoblasts, whereas CD55 was only detected on approximately 30% of the cells. Inhibition of CD46 and CD59 resulted in increased susceptibility of syncytiotrophoblasts to complement lysis. The protective function of CD55 could not be evaluated because of its reduced expression on isolated trophoblasts. These results suggest that syncytiotrophoblasts may be killed by complement and that membrane regulators to some extent protect these cells from complement damage.
The fifth C component (C5) exhibits a different stability when bound to sheep E or Escherichia coli 0111:B4, being fairly stable on the bacterial intermediate sensitized E. coli 0111:B4 coated with C components up to C5 (BAC1-5) and extremely labile on the RBC intermediate sensitized sheep E coated with C components up to C5 (EAC1-5). We examined the possibility that molecular changes of membrane-bound C5 might be responsible for the different functional behavior of the two intermediates using mAb to C5 and sensitive immunoassays to detect bound C5. The decay of EAC1-5 over 30 min of incubation at 37 degrees C was associated with a significant drop in the reactivity of bound C5 with three of four mAb used. These results contrasted with those obtained with BAC1-5, which showed unchanged reactivity with all mAb tested over the same period of incubation. The effect of mAb on the activity of C5 was then investigated in an attempt to relate the change of the reactivity pattern of EAC1-5 with the functional modification of bound C5. MAb 1.5 and 1.6 were the only antibodies that interfered with the functional activity of C5, although through a different mechanism. In particular, mAb 1.5 was active both on fluid-phase and on membrane-bound C5 and is therefore likely to interact with the binding site for the late components on C5. Conversely, mAb 1.6 was only effective on fluid-phase C5 and acted by promoting a decay of BAC1-5 similar to the spontaneous decay of EAC1-5. We suggest that the bacterial outer membrane may protect C5 from functional decay and that mAb 1.6 interferes with the stabilizing effect of the bacteria in an as yet unclear manner.
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