Transcriptomic signatures of antibody mediated rejection in early biopsies with negative histology in HLA incompatible kidney transplantation

Presensitized patients with circulating donor-specific antibodies (DSA) prior to transplantation are at risk for antibody-mediated rejection (ABMR). Peritransplant desensitization mitigates but does not eliminate the alloimmune response. We examined the possibility that subthreshold ABMR activity undetected by histology could be operating in some early biopsies. Whole-genome mRNA profiling was performed with Affymetrix microarrays in 30 kidney transplant biopsies, retrospectively selected from all biopsies performed within the first month with available MMDx reports. Kidney allograft biopsy transcriptome in presensitized patients (DSA+) who had received desensitization and did not develop active or probable ABMR by histology (R-/DSA+, n=10) was compared with biopsies showing active/probable ABMR (R+/DSA+, n=5). As negative controls, biopsies without rejection by histology performed within the identical time frame in patients without donor-specific antibodies at transplantation (R-/DSA-, n=15) were used .