Señales Moleculares de Rechazo en el Rechazo Crónico-Activo Mediado por Células T: Asociaciones Histológicas e...

Chronic-active T-cell-mediated rejection (caTCMR) remains debated and molecular diagnostics might aid risk-stratification. This retrospective two-center observational study analyzed 26 kidney allograft biopsies with caTCMR comparing them to 40 borderline/acute TCMR-cases (without caTCMR) and 308 subthreshold/negative controls after excluding microvascular inflammation (MVI) at/above threshold and overlapping pathologies. All biopsies received transcriptomic evaluation through microarray-based gene expression profiling. caTCMR-cases with acute TCMR (n=8) showed higher molecular TCMR activity (median TCMR_prob 0.54 [0.30-0.83]) than "pure" caTCMR (n=11; TCMR_prob 0.03 [0.01-0.28], p=0.012) or caTCMR with borderline TCMR (n=7; TCMR_prob 0.01 [0.01-0.77], p=0.036). TCMR_prob was low in subthreshold/negative controls but elevated in acute TCMR, BK virus nephropathy- and pyelonephritis-cases (side cohort). Molecular sign-outs classified 4/11 (36%) "pure" caTCMR-cases as molecular TCMR. Within the TCMR continuum (26 caTCMR plus 40 borderline/acute TCMR), i-, t- and ti-lesions were associated in univariable analyses with TCMR_prob >0.2, while i-IFTA/t-IFTA correlated with molecular chronicity. 7/26 (27%) caTCMR- and 7/40 (18%) borderline/acute TCMR-cases showed mixed molecular rejection activity above thresholds. In conclusion, significant molecular TCMR activity was present in a subset of caTCMR-cases and was associated with higher i/t/ti scores and, at times, molecular AMR signals, even with MVI<2. To confirm these preliminary observations, future studies and external validation are needed.