*Purpose: Allo-antigen-specific T-cytotoxic memory cells (TcM) which express CD40 ligand (CD154) in overnight lymphocyte co-culture are strongly associated with acute cellular rejection (ACR) seen in “for cause” biopsies for renal allograft dysfunction. Specifically, when the likelihood of rejection is increased, donor-specific allospecific TcM exceed those induced by HLA-non-identical third-party cell by 1.15-fold or greater.

*Methods: The performance of allospecific TcM was evaluated retrospectively in primary kidney transplant recipients at routine clinical visits, cross-sectionally at presentation for biopsies, and serially. Performance metrics were sensitivity, specificity, positive and negative predictive values.

*Results: Median age of 22 patients was 45 years (range 19-72), and included 13 males. The distribution of African american: Caucasian: Hispanic races was 13: 7: 1, and of deceased donors: donations after cardiac death (DCD): living donors was 13: 7: 1. The first sample was obtained at median 174 days (19-3481) after transplantation. 22 samples including single samples from 18 patients, and the first of several serial samples from each of four patients were analyzed. Six patients experienced biopsy proven ACR. A seventh showed BK virus nephropathy at biopsy for allograft dysfunction and circulating donor-specific anti-HLA antibodies (DSA), which improved with intravenous immune globulin. Of these seven patients with ACR or DSA, six demonstrated increased likelihood of rejection with allospecific TcM or a positive test (sensitivity 83%). Of the 15 remaining patients, 12 had no ACR clinically, while biopsies in the remaining three showed acute tubular necrosis (ATN) in one and stage II and III BK nephropathy in two recipients of DCD allografts. Ten of these 15 patients with no rejection had a negative test or decreased likelihood of rejection (specificity 67%). Five patients showed false positive tests, one with no-rejection, a second with ATN, and three with DCD allografts, of whom two had BK nephropathy. Positive and negative predictive values were 54% and 91% respectively. Serum creatinine at the end of follow-up was higher in 11 patients with positive tests compared with 11 patients with negative tests (1.7±0.7 vs 2.3±1.1, mg/dl, p=0.126, NS).

*Conclusions: Allospecific T-cytotoxic memory cells distinguish primary kidney recipients with quiescent allografts from those with dysfunction. Especially, as serial surveillance measure, this test system can facilitate decisions to manage immunosuppression

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