Table 3.
Rejection-related parameters – cohort 1 (BORTEJECT).
| Parameters | DSA+ patients | KLRC2 wt/wt | KLRC2 wt/del | P - value |
|---|---|---|---|---|
| n=86 | n=69 | n=17 | ||
| DSA characteristics | ||||
| HLA class I DSA, n (%) | 27 (31) | 21 (30) | 6 (35) | 0.77 |
| HLA class II DSA, n (%) | 42 (49) | 35 (51) | 7 (41) | 0.59 |
| HLA class I+II DSA, n (%) | 17 (20) | 13 (19) | 4 (24) | 0.74 |
| MFI of the immunodominant DSA, median (IQR) | 2,952 (1,476–7,454) | 3,470 (1,755–9,698) | 1,474 (1,173–2,188) | 0.005 |
| DSA number, median (IQR) | 1 (1–2) | 1 (1–2) | 1 (1–2) | 0.46 |
| Renal allograft biopsy results a | ||||
| Banff 2017 categories | ||||
| ABMR, n (%) | 50 (58) | 45 (65) | 5 (29) | 0.012 |
| C4d-positive ABMR, n (%) | 24 (28) | 22 (32) | 2 (12) | 0.13 |
| Active ABMR, n (%) | 15 (17) | 14 (20) | 1 (6) | 0.28 |
| Chronic active ABMR, n (%) | 33 (38) | 30 (44) | 3 (18) | 0.057 |
| cg without current/recent Ab interaction, n (%) | 2 (2) | 1 (1) | 1 (6) | 0.36 |
| Banff borderline lesion, n (%) | 9 (11) | 6 (9) | 3 (18) | 0.37 |
| ABMR-related single lesions | ||||
| ptc scoreb, median (IQR) | 0 (0–2) | 1 (0–2) | 0 (0–0) | 0.002 |
| g score b , median (IQR) | 1 (0–2) | 1 (0–2) | 0 (0–1) | 0.026 |
| g+ptc score, median (IQR) | 2 (0–3) | 2 (0–4) | 0 (0–1) | 0.002 |
| cg scoreb, median (IQR) | 0 (0–1) | 0 (0–1) | (0 (0–0) | 0.072 |
| TCMR-related single lesions | ||||
| t score, median (IQR) | 0 (0–0) | 0 (0–0) | 0 (0–0) | 0.45 |
| i score, median (IQR) | 0 (0–0) | 0 (0–0) | 0 (0–1) | 0.13 |
| MMDx analysis c | ||||
| Archetypal analysis | ||||
| ABMR archetype, n (%) | 41 (49) | 37 (56) | 4 (24) | 0.028 |
| Early onset ABMR, n (%) | 13 (16) | 10 (15) | 3 (18) | 0.72 |
| Fully active ABMR, n (%) | 24 (29) | 23 (35) | 1 (6) | 0.018 |
| Late ABMR, n (%) | 4 (4.8) | 4 (6.1) | 0 (0) | 0.58 |
| TCMR archetype, n (%) | 1 (1) | 0 (0) | 1 (6) | 0.21 |
| No rejection archetype, n (%) | 41 (49) | 29 (44) | 12 (71) | 0.061 |
| Rejection classifier | ||||
| ABMRpm score c , median (IQR) | 0.36 (0.10–0.65) | 0.41 (0.14–0.72) | 0.10 (0.07–0.27) | 0.001 |
| TCMR score c , median (IQR) | 0.03 (0.02–0.04) | 0.03 (0.02–0.04) | 0.03 (0.02–0.04) | 0.91 |
| All rejection score c , median (IQR) | 0.46 (0.13–0.75) | 0.49 (0.17–0.78) | 0.15 (0.07–0.52) | 0.01 |
| Pathogenesis-based transcript (PBT) scores | ||||
| NK cell burden-associated (NKB), median (IQR) | 0.74 (0.43–1.31) | 0.97 (0.50–1.35) | 0.56 (0.32–0.87) | 0.017 |
| IFN-γ-associated (GRIT1), median (IQR) | 0.70 (0.31–0.97) | 0.79 (0.39–1.0) | 0.44 (0.08–0.70) | 0.005 |
| T cell burden (TCB), median (IQR) | 1.29 (0.91–1.91) | 1.29 (0.98–1.94) | 1.42 (0.63–1.67) | 0.42 |
| Macrophage-associated transcripts | ||||
| QCMAT, median (IQR) | 0.35 (0.19–0.57) | 0.41 (0.22–0.61) | 0.22 (0.10–0.40) | 0.032 |
| AMAT1, median (IQR) | 0.41 (0.19–0.63 | 0.45 (0.21–0.65) | 0.28 (-0.06–0.49) | 0.099 |
ABMR, antibody-mediated rejection; cg, glomerular basement membrane double contours; DSA, donor-specific antibody; g, glomerulitis; IFN-γ, interferon-gamma; IQR, interquartile range; MFI, mean fluorescence intensity; MMDX, Molecular Microscope Diagnostic System; NK cell, natural killer cell; ptc, peritubular capillaritis; TCMR, T cell-mediated rejection.
a
Morphologic lesions were scored according to the Banff 2017 classification of renal pathology.
b For 2, 4 and 5 recipients, biopsy material was not sufficient for ptc, g and cg scoring, respectively.
c
Gene expression analysis was performed in 83 of the 86 study patients.