Date: Tuesday, May 2, 2017
Session Name: Poster Session D: Kidney: Acute Cellular Rejection
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall D1
The clinical significance of early histological BBC in kidney transplant recipients (KTR) is unclear. It is also unknown if biomarkers predict progression to acute rejection vs. spontaneously regression. 154/372 KTRs (3mo & 1yr protocol Bx) transplanted between dates 1/13-11/14 with BBC (27%; 42/154) vs. normal (NL) histology (73%; 112/154) were prospectively analysed for progression by 1yr. In comparison to NL, KTR with BBC at 3mo had similar rates of BBC at 1yr (36% vs. 28%), but markedly increased progression to TCMR≥Banff1A (41%vs.14%, p=0.0001). Conversely, more KTR with NL at 3mo were NL at 1yr compared to those with 3mo BBC (58% vs. 23%, p=0.001). Further, KTR with 3mo BBC have significantly higher creatinine at 24mo (1.73 vs.1.49, p=0.04) and chronicity scores at 1yr (2.9 vs.2.2, p=0.006), compared to those with NL. Importantly, in KTRs with 3mo BBC, those with persistent BBC/progression (TCMR) at 1yr had significantly worse chronicity scores (ct+cv+ci) at 1yr (3.21 vs. 1.45, p=0.0002), IF+i positivity (78% vs. 0%, p<0.0001) and renal dysfunction at 2yrs (creatinine: 1.9 vs.1.28, p=0.02), compared to those whose inflammation resolved. Thus, in KTR with 3mo BBC, persistence/progression of inflammation at 1yr increases risk for adverse graft outcomes. Clinical factors (e.g. DGF, de novo DSA, sCr, & histology at 3mo) could not predict progression/persistence vs. resolution. Based on our finding that B cell cytokine expression profiles (after CD40L/CpG stimulation) predict rejection, we asked if IL-10:TNFa expression ratio within transitional B cells (TrB) could predict progression/persistence vs. resolution of 3mo BBC. PBMCs were available for 28/42 KTR with 3mo BBC. Of these 28, 10 resolved, and 18 persisted/progressed by 1yr. IL-10:TNFa ratio in TrBs (0.73 vs. 2.46, p=0.02) and in the most immature “T1” TrB cells (1.42 vs. 4.84, p=0.01) were significantly reduced in patients with persistence/progression vs. resolution, indicating a more pro-inflammatory cytokine profile. Importantly, the T1 IL-10/TNFa ratio strongly predicted progression/persistence in KTR with 3mo BBC (AUC 0.875; p=0.001; sensitivity 93% specificity 80%).
Conclusion: KTR with early BBC that exhibit either progressive/persistent tubulointerstitial inflammation at 1yr represent a high-risk cohort for graft dysfunction. This group might be predicted early by the T1 B cell IL-10:TNFa ratio at 3mo. This finding and its clinical utility must now be validated in a bigger cohort.
CITATION INFORMATION: Cherukuri A, Sharma A, Mehta R, Hariharan S, Rothstein D. Persistence/Progression of Early Banff Borderline Changes (BBC) Is Associated with Chronic Renal Allograft Damage and Can Be Predicted by B Cell Cytokine Profile. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Cherukuri A, Sharma A, Mehta R, Hariharan S, Rothstein D. Persistence/Progression of Early Banff Borderline Changes (BBC) Is Associated with Chronic Renal Allograft Damage and Can Be Predicted by B Cell Cytokine Profile. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/persistenceprogression-of-early-banff-borderline-changes-bbc-is-associated-with-chronic-renal-allograft-damage-and-can-be-predicted-by-b-cell-cytokine-profile/. Accessed April 2, 2020.
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