Acute antibody-mediated rejection in presence of MICA-DSA and successful renal re-transplant with negative-MICA virtual crossmatch

Abstract

Aim The polymorphic MICA molecules, which are expressed on the surface of vascular endothelial cells, might be antigenic targets for antibody mediated rejection (AMR), As a well-documented case of acute rejection due to antibodies against MICA has not been reported, in this study, we provided that a virtual crossmatch for MICA, performed in addition to the HLA histocompatibility assay, will benefit kidney transplant recipient with sensitization of MICA antigens. Methods Sequencing based typing for MICA was performed on donors and recipient. MICA antibodies were tested by single antigen Luminex bead array prepared in our own laboratory. Flow crossmatch and random endothelial cell crossmatch were performed. We determined whether the patient had MICA-DSA for a given donor by performing MICA genotyping of donor. The algorithm of MICA virtual crossmatch was based on the results of missed MICA allele or alleles of a given donor and the specificity of MICA antibodies in recipient’s serum. Results We describe the incidence of acute C4d+ AMR in a patient who had received a first kidney transplant with a zero HLA antigen mismatch. Retrospective analysis of post-transplant T and B cell crossmatches were negative, but a high level of MICA alloantibody was detected in sera collected both before and after transplant. The DSA against the first allograft mismatched MICA*018 was in the recipient. Flow cytometry and cytotoxicity tests with five samples of freshly isolated human umbilical vein endothelial cells demonstrated the alloantibody nature of patient’s MICA-DSA. Prior to the second transplant, a MICA virtual crossmatch and T and B cell crossmatches were used to identify a suitable donor. The patient received a second kidney transplant, and allograft was functioning well at one-year follow-up. Results Our study indicates that MICA virtual crossmatch is important in selection of a kidney donor if the recipient has been sensitized with MICA antigens.