Molecular diagnosis of antibody-mediated rejection: evaluating biopsy-based transcript diagnostics in the presence of donor-specific antibodies but without microvascular inflammation, a single center descriptive analysis

Biopsy-based transcript diagnostics may identify molecular antibody-mediated rejection (AMR) when microvascular inflammation (MVI) is absent. In this single-center cohort, biopsy-based transcript diagnostics were validated in 326 kidney allograft biopsies. 71 histological AMR and 35 T-cell mediated rejection (TCMR) cases were identified as molecular AMR and TCMR in 55% and 63%, respectively. Among 121 cases without MVI (g+ptc=0), 45 donor-specific antibody (DSA)-positive (37%) and 76 DSA-negative cases (63%) were analyzed. 21/121 (17%) cases showed borderline changes or TCMR, while BK nephropathy was excluded. None of the 45 DSA-positive patients showed molecular AMR. Among 76 DSA-negative patients, two had mixed molecular AMR/TCMR. The all AMR phenotype score (sum of R4-R6) exhibited median values of 0.13 and 0.12 for DSA-positive and DSA-negative patients, respectively (p=0.84). 6/45 (13%) DSA-positive and 8/76 (11%) DSA-negative patients showed an all AMR phenotype score >0.30 (p=0.77). Patients with a higher all AMR phenotype score showed 33% more histological TCMR (p=0.005). The median all AMR phenotype scores of glomerular basement membrane double contours (cg)=0 and cg>0 biopsies were 0.12 and 0.10, respectively (p=0.35). Biopsy-based transcript diagnostics did not identify molecular AMR in cases without MVI. Follow-up biopsies and outcome data should evaluate the clinical relevance of sub-threshold molecular alterations.