Update on C1 Esterase Inhibitor in Human Solid Organ Transplantation

Transplantation. 2019 Sep;103(9):1763-1775. doi: 10.1097/TP.0000000000002717.

Abstract

Complement plays important roles in both ischemia-reperfusion injury (IRI) and antibody-mediated rejection (AMR) of solid organ allografts. One approach to possibly improve outcomes after transplantation is the use of C1 inhibitor (C1-INH), which blocks the first step in both the classical and lectin pathways of complement activation and also inhibits the contact, coagulation, and kinin systems. C1-INH can also directly block leukocyte-endothelial cell adhesion. C1-INH contrasts with eculizumab and other distal inhibitors, which do not affect C4b or C3b deposition or noncomplement pathways. Authors of reports on trials in kidney transplant recipients have suggested that C1-INH treatment may reduce IRI and delayed graft function, based on decreased requirements for dialysis in the first month after transplantation. This effect was particularly marked with grafts with Kidney Disease Profile Index ≥ 85. Other clinical studies and models suggest that C1-INH may decrease sensitization and donor-specific antibody production and might improve outcomes in AMR, including in patients who are refractory to other modalities. However, the studies have been small and often only single-center. This article reviews clinical data and ongoing trials with C1-INH in transplant recipients, compares the results with those of other complement inhibitors, and summarizes potentially productive directions for future research.

Publication types

  • Review

MeSH terms

  • Allografts
  • Animals
  • Complement Activation / drug effects*
  • Complement C1 Inhibitor Protein / adverse effects
  • Complement C1 Inhibitor Protein / therapeutic use*
  • Complement C1s / antagonists & inhibitors*
  • Complement C1s / immunology
  • Complement Inactivating Agents / adverse effects
  • Complement Inactivating Agents / therapeutic use*
  • Delayed Graft Function / immunology
  • Delayed Graft Function / prevention & control*
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control*
  • Graft Survival / drug effects
  • Humans
  • Organ Transplantation* / adverse effects
  • Reperfusion Injury / immunology
  • Reperfusion Injury / prevention & control*
  • Risk Factors
  • Treatment Outcome

Substances

  • Complement C1 Inhibitor Protein
  • Complement Inactivating Agents
  • Complement C1s