Fig. 3.

Predicted probability of TCMR and kidney function in rejectors and stable or non-rejector controls and in patients with BK virus nephropathy.

a – median of the set of probabilities of T-cell-mediated rejection (TCMR) estimated for each patient of the development dataset in the 50 repeats of the cross-validation cycles (Step 12 of Note 1 in Supplementary Discussion); (b–e) – predicted probability of TCMR, based on the newly-developed seven-gene signature (Supplementary Fig. S5); (f–k) – estimated glomerular filtration rate (eGFR), based on the MDRD4 equation; ABMR – antibody-mediated rejection (category 2 according to Banff’09 classification); TCMR – T-cell-mediated rejection (category 4); Mixed – histological features of both, ABMR and TCMR; TCMR+ – patients with TCMR alone and with mixed-type histology; BKVN – BK virus nephropathy (confirmed with a specialised histological staining); Stable – patients fulfilling the inclusion and exclusion criteria listed in Table 1; Non-rejector – patient not fulfilling the selection criteria in Table 1 but without evidence of TCMR, ABMR or BKVN up to day 400 post-transplantation; dot colour: black – rejectors, grey – stable or non-rejector patients; dot shape – induction agent in KALIBRE patients: circle – Basiliximab, triangle – Rituximab, square – Alemtuzumab; dotted lines – cut-off 0·5 for dichotomous classification of the probability of TCMR (a-e) and median eGFR (71.8 mL/min/1.73m²) of the summary of stable patients in the discovery signature-development dataset (F—K); samples: rejectors – single pre-biopsy sample, BKVN – single near-biopsy sample, stable/non-rejector patients – summary (median per patient) of longitudinal samples covering between days four and 400 post transplantation; Discovery (a,f) – training patients used in TCMR signature development (TCMR (n = 27) fulfilling the inclusion and exclusion criteria listed in Table 1 and stable patients (n = 27)); Validation (b,g) – test patients from the KALIBRE study used for TCMR signature validation (Mixed-type rejectors (n = 9) and new stable patients (n = 17)); External (c,h) – patients from the independent trial EMPIRIKAL used for TSMR signature validation (rejectors (n = 9) with TCMR or Mixed-type histology, non-rejectors (n = 15)); PreTx (d,i) – cross-sectional pre-transplantation samples – one per patient from rejectors with TCMR (n = 16) and Mixed-type (n = 2) histology and training stable patients from the signature development dataset (n = 20)); e,h – ABMR rejectors (n = 5), RitCam rejectors with alternative induction and TCMR (n = 6) or Mixed-type histology (n = 2); BKVN patients: grey dots BKVN (n = 7) included in the BKVN signature development dataset, crossed dots BKVN: +dot (n = 2) excluded from the training dataset due to prior suspected TCMR or some genes missing, x-dot (n = 1) Alemtuzumab induction, x (n = 1) patient from the EMPIRICAL trial; p-values derived from a Wilcoxon-Mann-Whitney tests.