HoloGRAFT™

We are ready to invite external laboratories to participate in the evaluation of HoloGRAFT™. Join our Clinical Research Program and evaluate measuring the absolute concentration of donor-derived cfDNA with HoloGRAFT™ as a biomarker for graft injury in your own lab.

The HoloGRAFT™ Screening Plates, Monitoring Assays and HoloGRAFT™ Software meet the needs of any research application that requires highly sensitive detection and quantification of graft-derived, cell-free DNA after organ transplantation.

HoloGRAFT uses copy number variant markers, stretches of DNA inherited in zero, one or two-copy forms. The donor-informative markers, as well as their detected amplicons, are missing in the patient. The detected amplicons are subsets of the variants, in contrast to SNP-based alternatives, where the variants are subsets of the detected amplicons. Therefore, HoloGRAFT is the only cfDNA method with a negative background.

• The use of donor-derived cell-free DNA (dd-cfDNA) is evidence-based and validated, and a prime example of much-needed innovation in transplant organ surveillance. It has demonstrated utility in the early detection of allograft injury and assistance with clinical decision-making regarding allograft biopsy and treatment initiation.
• Dd-cfDNA is a better discriminator of acute kidney rejection than serum creatinine. (Bloom et al, 2017) [1]
• Elevated dd-cfDNA levels are associated with an increased likelihood of de novo DSA development in kidney recipients. (Jordan et al. 2018)[2]
• Elevated dd-cfDNA levels are found to predict longitudinal eGFR decline, while normal levels did not have evidence of eGFR decline during the period of study follow-up. (Stites et al. 2020)[3]
• The accumulated evidence supporting the use of dd-cfDNA argues that its use should no longer be considered investigational. (ASTS Position Statement)[4]

[1] Bloom RD, Bromberg JS, Poggio ED, et al. Cell-free DNA and active rejection in kidney allografts. JASN. 2017;28:2221-2232.

[2] Jordan SC, Bunnapradist S, Bromberg JS, et al. Donor-derived cell-free DNA identifies antibodymediated rejection in donor specific antibody positive kidney transplant recipients. Transplant Direct. 2018. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133406/.

[3] Stites E, Kumar D, Olaitan O, et al. High levels of dd-cfDNA identify patients with TCMR 1A and borderline allograft rejection at elevated risk of graft injury. Am J Transplant. 2020;20:2491-2498 PMID 32056331.

[4] ASTS Statement on donor-derived cell-free DNA (dd-cf-DNA) Approved by the ASTS Executive Committee on March 6, 2023  https://asts.org/docs/default-source/position-statements/dd-cfdna-position-statement.pdf

The HoloGRAFT™ System consists of DNA Screening plates, 43 individual monitoring assays, dPCR Master Mix, and HoloGRAFT™ Software. The HoloGRAFT™ Copy Number Variant (CNV) Assays are a set of 43 genetic markers that are able to differentiate, and then quantify, donor-derived DNA. HoloGRAFT™ Software guides the user through reaction set-up for both screening and quantification and analyzes the collected data. The procedure for determining the amount of donor-derived cfDNA in a sample consists of two parts: a Screening test and a monitoring test.

The presence or absence of copy-number variant markers in the recipient and the donor is determined using a HoloGRAFT™ Screening Plate. A donor-informative assay measures a marker that is present (positive) in the donor and absent (negative) in the recipient’s genome.