In a study of cardiac bypass (valve replacement) patients with Dr Colin Hamilton-Davies (Middlesex Hospital ICU, London) we have found that low pre-operative IgM or IgG EndoCAb indicates a greater risk of poor outcome. EndoCAb levels are expressed as median-units (MU), a percentage of the median of normal adult levels (100 = median) for each Ig class of antibody. Patients at or above median levels of EndoCAb had a normal outcome.
(Manuscript submitted)
In a previous study (see Mythen et al, 1993) it was found that high pre-operative IgG EndoCAb was associated with retention of gut mucosal pH and a good outcome following bypass surgery. In this context, see also Soong et al, 1997. The following figure is from the Mythen (1993) study:
We believe that during cardiac bypass the blood flow to the gut is reduced. The resulting gut ischaemia enables translocation of endotoxin from the gut into the circulation. In a number of studies we have seen a consistent drop in postoperative circulating EndoCAb from the preoperative value and have interpreted this as consumption of EndoCAb by systemic release of endotoxin. We hypothesis that if patients' pre-operative EndoCAb is low, even moderately low, they may not be able to cope with this efflux of endotoxin, which may have mild to severe clinical consequences. If the drop in EndoCAb is clinically important, it may be that clinical intervention is possible by immunoprophylaxis to raise the EndoCAb levels of patients in the at risk group.
The blood donor population can be screened with the EndoCAb ELISA for individuals with high natural EndoCAb IgG - a cut-off of 400MU was used, so donors were at least 4 times greater than median levels. The resultant hyperimmune IVIG made from their plasma was 8 times greater in EndoCAb than normal IVIG. While such donors represent less than 4% of the population, their high EndoCAb levels persist for years, allowing repeated plasmapheresis (we do not know why these individuals express such high EndoCAb levels)
A phase-1 trial was conducted of infusion of EndoCAb IVIG in 9 septic shock patients in ICU (in collaboration with G Ramsay, J Reidy, S Boom: Glasgow (unpublished)). Patients tolerated the infusions, and IgG EndoCAb was raised - almost to hyperimmune levels. Anti-TT from the infused IVIG was measured as a bystander antibody, while IgM EndoCAb reflected patients' autologous EndoCAb kinetics. The trial was too small to infer anything about efficacy, but there was at least one anecdotal miracle cure.
While manufacture of EndoCAb hyperimmune IVIG entails a large effort and cost, it may be possible to examine efficacy of passive administration of EndoCAb by infusion of EndoCAb hyperimmune plasma. We have noted that low EndoCAb indicates an at risk patient group for cardiac bypass surgery (above). We have conducted a phase-1 trial of prophylactic administration of IgG-EndoCAb hyperimmune FFP in patients with low preoperative EndoCAb
See Hamilton-Davies et al (Vox Sang 1996) References