Theory 03/Transplant & Immune Tolerance/Xenotransplantation
Xenograft Survival Is a Complement Ratio
Survival is predicted from antibody. The destruction may be done by the recipient's complement, regulated by the donor's surface.
The survival of a xenograft is set by the ratio of donor complement regulators to recipient complement activity rather than by antibody titre, so a lower-titre recipient can reject faster if its complement is more active.
01The evidence
Xenografts fail within minutes to days despite antibody depletion protocols, and survival improves when human complement regulators are expressed on the donor endothelium.
02The tension
The field measures antibody and depletes it. Survival improves but remains short, which suggests the rate-limiting step is the regulator-complement balance rather than the initiating antibody.
03The mechanism
Complement is regulated on the cell surface by membrane cofactor proteins. A donor organ carries its own regulators, which are species-specific and therefore poor at controlling recipient complement.
That makes the ratio of donor regulator efficacy to recipient complement activity the determinant, and predicts that engineering regulator expression should extend survival more than antibody depletion at matched titre.
04What this is not
Those predict from circulating antibody. This predicts from surface regulation against complement, which explains failure at low titre.
05Predictions
- P1Survival should track the regulator ratio.
- P2Regulator expression should extend survival at constant titre.
- P3Recipients with higher complement activity should reject faster.
06Refutation
Survival tracking antibody titre at controlled regulator expression would restore the titre model.
07What it changes
It would target regulator engineering rather than antibody removal.