Micromolar A and B blood group active trisaccharides abolish human complement haemolytic activity assayed by erythrocytes.
BACKGROUND
At present, there is really no satisfactory treatment of severe haemolytic transfusion reactions involving the ABO system other than the use of steroids that at best are palliative in their effects. In contrast, the use of micromolar concentrations of A or B blood group active trisaccharides that are inexpensive and readily available may prevent lysis by generating soluble immune complexes (ICs) that consume complement. The purpose of this study was to determine the total lytic activity of human serum and to estimate the extent to which trisaccharides can exhaust this capacity.


METHODS
We measured complement consumption by (ICs) formed between anti-blood group antibodies and A or B blood group active sugars on erythrocytes (solid phase) or soluble components carrying trisaccharides (fluid phase) in AB serum. A direct complement-mediated lysis (DCL) assay measured the solid-phase reaction and an indirect complement consumption assay (CCA) allowed determination of the fluid-phase reaction. In CCA, the residual lytic activity of AB serum was measured following preincubation with various ICs.


RESULTS
Based on over 4000 data points a new mathematical model of complement consumption was formulated. Its predictions deviated by less than 6% in DCL and 9% in CCA when compared with the experimentally accessible data. The new model describes the dynamics of complement consumption including the soluble phase of the reaction.


CONCLUSIONS
The mathematical model extrapolation predicts that: (1) in undiluted human serum up to 40% of the physiological erythrocyte concentration could be lysed (when antibodies did not limit lysis); and (2) a 40 microM (or less) concentration of blood group active trisaccharides per patient is sufficient to block the haemolytic complement activity.
Bakács
Tibor
T
Department of Probability, Rényi Alfréd Institute of Mathematics, Hungarian Academy of Sciences, Budapest, Hungary.
Szabó
Miklós
M
Varga
László
L
Mushens
Rosey
R
Mehrishi
Jitendra N
JN
Lutz
Hans U
HU
Merry
Tony H
TH
Tusnády
Gábor
G
D000017:ABO Blood-Group System / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal; D003165:Complement System Proteins / Q000378:metabolism*; D004912:Erythrocytes / Q000276:immunology; D006461:Hemolysis; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D018448:Models, Immunological; D008962:Models, Theoretical; D014312:Trisaccharides / Q000097:blood*
D000017:ABO Blood-Group System; D000911:Antibodies, Monoclonal; D014312:Trisaccharides; D003165:Complement System Proteins