Method of improving transplant function using soluble complement receptor type I (sCR1)
A method is disclosed for inhibiting complement activation in brain-dead organ donors, particularly kidney donors, which leads to improvement of organ function of transplanted organs in recipients. The method involves administration of a complement inhibitory protein, specifically a soluble complement receptor type I (sCR1) polypeptide to the donor prior to harvesting the organ for transplant.
1. A method for preparing a transplant organ from a brain-dead organ donor to improve organ function in a recipient of said transplanted organ from said brain-dead organ donor, said method comprising administering to a brain-dead mammalian donor an effective amount to inhibit systemic and/or local complement activation of a soluble complement receptor type I (sCR1) polypeptide prior to excision of said organ from said donor.
2. A method for improving transplant organ function in a transplant organ recipient comprising:
administering to a brain-dead organ donor an amount of a soluble CR1 polypeptide effective to inhibit systemic and/or local organ donor complement activation;
removing an organ from said brain-dead organ donor; and
transplanting said organ into a recipient.
3. A method of treating transplant organ rejection in a recipient of a transplant from a brain-dead organ donor, said method comprising administering to said brain-dead mammalian donor an effective amount of a soluble complement receptor type I (sCR1) polypeptide.
4. The method according to any of claims 1 - 3 , wherein said sCR1 polypeptide is selected from the group consisting of a fragment of human CR1 comprising at least short consensus repeats 8-11;
a fragment of human CR1 comprising at least short consensus repeats 15-18;
a soluble CR1 polypeptide comprising human CR1 short consensus repeats 8-11 and 15-18;
a fragment of human CR1 comprising long homologous repeat B;
a fragment of human CR1 comprising long homologous repeat C;
a fragment of human CR1 comprising long homologous repeats B and C;
a fragment of human CR1 comprising long homologous repeats B, C and D;
a fragment of human CR1 comprising at least long homologous repeats A and B;
a fragment of human CR1 comprising long homologous repeats A, B and C;
a fragment of human CR1 comprising long homologous repeats A, B, C and D;
a fragment of human CR1 comprising the extracellular domain of CR1;
a fragment of human CR1 comprising the extracellular domain of CR1 and having the N-terminal LHR A deleted (sCR1 [desLHR-A]);
a soluble CR1 polypeptide having modified glycosylation to improve serum half-life in vivo;
a soluble CR1 polypeptide having glycosylation modified to exhibit sialyl Lewis X moieties (sCR1-sLe x );
a soluble CR1 construct having two or more CR1 polypeptide moieties linked to a carrier molecule; and
combinations thereof.
5. The method according to claim 4 , wherein said sCR1 polypeptide is administered by an intradermal, intramuscular, intraperitoneal, intravenous, intra-arterial, subcutaneous, intrathecal, epidural, oral or pulmonary route.
6. The method according to claim 5 , wherein said organ is selected from the group consisting of liver, kidney, heart, and lung.
7. The method according to claim 6 , wherein said organ is a kidney.