Low-MFI (median fluorescence intensity) pre-transplant DSA (donor specific antibodies) leading to anamnestic antibody mediated rejection in live-related donor kidney transplantation

In solid organ transplantation, the compatibility between recipient and donor relies on testing prior to transplantation as a major determinant for the successful transplant outcomes. This compatibility testing depends on the detection of donor-specific antibodies (DSAs) present in the recipient. Indeed, sensitized transplant candidates are at higher risk of allograft rejection and graft loss compared to non-sensitized individuals. Most of the laboratories in India have adopted test algorithms for the appropriate risk stratification of transplants, namely: 1) donor cell-based flow-cytometric cross-match (FCXM) assay with patient's serum to detect DSAs; 2) HLA-coated beads to detect anti-HLA antibodies; and 3) complement-dependent cytotoxicity crossmatch (CDCXM) with donor cells to detect cytotoxic antibodies. In the risk stratification strategy, laboratories generally accept a DSA median fluorescence index (MFI) of 1000 MFI or lower MFI (low-MFI) as a negative value and clear the patient for the transplant. We present two cases of live-related donor kidney transplants (LDKTs) with low-MFI pretransplant DSA values who experienced an early acute antibody-mediated rejection (ABMR) as a result of an anamnestic antibody response by DSA against HLA class II antibodies. These results were confirmed by retesting of both pre-transplant and post-transplant archived sera from patients and freshly obtained donor cells. Our examples indicate a possible ABMR in patients with low MFI pre-transplant DSA. Reclassification of low vs. highrisk may be appropriate for sensitized patients with low-MFI DSA.

Automated summary

In solid organ transplantation, compatibility testing prior to transplantation is crucial for successful outcomes. Indian laboratories have adopted test algorithms for risk stratification, but reclassification may be necessary for sensitized patients with low MFI DSAs. Our case studies suggest the possibility of antibody-mediated rejection in low MFI DSA patients.