Non-invasive diagnosis and prediction of acute rejection (AR) is a critical unmet need. A In a randomized multicenter trial of 222 renal transplant recipients a novel blood transcriptional assay, kSORT was evaluated for its accuracy in diagnosing and predicting biopsy confirmed AR.

Blood were drawn at day 0, 10, months 3, 6, 12 and at graft dysfunction for analysis of kSORT, a 17 gene assay (CFLAR, DUSP1, IFNGR1, ITGAX, MAPK9, NAMPT, NKTR, PSEN1,CEACAM4, EPOR, GZMK, RARA, RHEB, RXRA, SLC25A37, RNF130, RYBP) that provides AR high or low immune risk scores. The assay has a ~15% assay read out of intermediate scores where repeat sampling is recommended. Biopsies were done on all patients by protocol at engraftment and 12 months post-transplantation and when clinically indicated. The kSORT assay was run on 338 blood samples obtained from the first 79 enrolled patients, of which 98 blood samples were matched with protocol or indicated biopsies. 22 patients had clinically suspected acute rejection (AR) of which 18 were biopsy confirmed. RNA was extracted and QPCR for all 17 genes was normalized to 18S; data was profiled using a customized algorithm kSAS to produce an immune risk score for rejection.

Of the 18 biopsy confirmed AR episodes, all were cellular and DSA negative; 15 had definite kSORT scores and 3 were intermediate; 14/15 AR had high-risk KSORT scores. 11 AR episodes had prior blood samples collected per protocol in the previous 4 months; 8/11 of the pre-AR samples had high kSORT scores, in the absence of clinical graft dysfunction. Of the 80 biopsy matched blood samples without histological AR, 73 had definite kSORT scores, and 7 had intermediate calls. 67/73 blood samples matched with biopsies without AR, had low-risk kSORT scores. 13 blood samples were positive by BK QPCR, and 12/13 of these blood samples had low-risk scores for kSORT and 1 was intermediate.

Interim results of kSORT assay confirms that the assay has 93.3% sensitivity and 90% specificity and 98.6% NPV for the diagnosis of AR, and is not confounded by BK viremia. 73% of AR could have been diagnosed by the kSORT assay days-months prior their current time-line for diagnosis based on the serum creatinine alone, supporting the use of this assay for serial monitoring of rejection risk and proactive immunosuppression customization to alloimmune risk.

CITATION INFORMATION: Ekberg J, Jespersen B, Skov K, Sarwal M, Sigdel T, Hsieh S, Lindner P. A Non-Invasive Blood Transcriptional Assay, Ksort, Monitors Alloimmune Response in the Sailor Randomized Multicenter Trial. Am J Transplant. 2016;16 (suppl 3).

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