CUSTOMER SPOTLIGHT: Mid-South Transplant Foundation, Inc. C3d Validation and Implementation
For all histocompatibility laboratories, Complement-Dependent Cytotoxicity (CDC) testing proves to be time consuming and tedious when evaluating the efforts needed to QC reagents, prepare trays, and perform proficiency testing. Mid-South Transplant Foundation (MSTF) is a private, non-profit organ procurement organisation and HLA Laboratory, serving hospitals in Tennessee, Arkansas, and Mississippi.
In 2012 and 2014, transplant centres in MSTF's service are requested they evaluate C1q testing. In 2015, MSTF performed a validation study between C1q and C3d with acceptable results between both assays. Brett D. Loehmann, CHS and the team at MSTF subsequently decided to utilise the Immucor LIFECODES® C3d Detection Assay for clinical purposes.
The Classical Pathway is the most widely understood mode for complement activation and begins with the binding of the C1q portion of the C1 complex to the Fc portion of antibodies captured by antigens on the surface of cells. One of the downstream products of the cascade is C4d which covalently attaches near the site of activation and thus makes a good marker for detection of antibody-mediated rejection (AMR). C3d is formed at the end of the cascade and demonstrates that the cascade has gone to completion.
Furthermore, since C3d is downstream of C4d, if C3d is formed, C4d deposition is most likely to have occurred, supporting MSTF’s decision to use the C3d assay. Following a simple and straightforward validation, MSTF began stratifying antibodies as IgG+/C3d+ and IgG+/C3d- when reporting results to transplant centres. Currently, two transplant centres with whom MSTF partners are using the C3d assay for final antibody assignments. Physicians and surgeons that work closely with MSTF have grown to trust the results of the C3d assay such that IgG+/C3d+ antibodies are automatically deemed unacceptable in UNET. They anticipated this would increase their recipient’s access to potential transplant opportunities. To date, they have successfully transplanted 9 patients with IgG+/C3d- antibodies that would have previously been classified as unacceptable. These patients have not formed donor specific antibodies post-transplant and there has been no observed graft dysfunction or graft loss. For these HLA sensitised transplant candidates, identifying which antibodies are C3d complement fixing and which antibodies are not, has provided a pathway to transplantation.
“We believe that the LIFECODES C3d Detection kit is the best indicator of complement fixation that is currently on the market. We were already familiar with the LIFECODES Single Antigen Assay and MATCH IT! software so adding C3d Detection was easy.”
– Brett Loehmann, Histocompatibility Laboratory Manager/Supervisor