Effect of Peritransplant C3d Blockade and Ischemia on Chronic Rejection and Vasculopathy in an Experimental OMC FlapModel of VCA
Abstract
Based on observations that the complement protein C3d plays a pivotal role in the regulation of cell mediated immunity, we are hypothesizing that blockade of this protein early in the post-transplant period may mitigate rejection, and protect the graft from ischemia reperfusion injury (IRI). We are using our allogeneic rat VCA model to determine where C3d and its receptor CD21 binds in the allograft, and how that binding differs in titrated immunosuppression models designed to mimic severe acute cellular rejection (ACR), mild ACR and chronic rejection (CR). Interestingly, C3d binds in ACR, and binds first to structures within the hair follicle in the skin as well as vessels. CD21 expression in the graft increases significantly after C3d binding is evident. We have also started the cold ischemia groups and are assessing how IRI influences C3d and CD21 expression. We are producing bulk antibody from a cell line with an IgG-CD21 dimer and expect to start in vivo blockade experiments in the first quarter of year 2. The overall goal of the project is to reduce the amount of immunosuppression required to maintain VCA allografts, reducing the risk/benefit ratio and allowing wider access to VCA transplantation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1197725
Entities
People
- Christina Kaufman
Organizations
- University of Louisville