Article
作者: Kumar, Dhiren ; Dęborska-Materkowska, Dominika ; Prewett, Adam ; Gryczman, Marta ; Mackova, Martina ; Hruba, Petra ; Viklicky, Ondrej ; Baliga, Rajendra ; Hidalgo, Luis G ; Konopa, Joanna ; Myślak, Marek ; Demko, Zachary ; Gupta, Gaurav ; Gauthier, Philippe ; Sikosana, Majid L N ; Brennan, Daniel ; Pączek, Leszek ; Smykal-Jankowiak, Katarzyna ; Gill, Jagbir ; Slatinská, Janka ; Mazurkiewicz, Joanna ; Lee, Michelle ; Lowe, David ; Hughes, Peter ; Domański, Leszek ; Wiecek, Andrzej ; Bobba, Sindhura ; Fryc, Justyna ; Ciszek, Michał ; Bromberg, Jonathan ; Schachtner, Thomas ; Mueller, Thomas ; Shojai, Soroush ; Francis, Iman ; Banasik, Mirosław ; Kamal, Layla ; Kojc, Nika ; Vucur, Ksenija ; Weir, Matthew R ; Lan, James ; Perkowska-Ptasińska, Agnieszka ; Jittirat, Arskarapurk ; Debska-Ślizień, Alicja ; Patel, Anita ; Gill, John ; Glyda, Maciej ; Arnol, Miha ; Moinuddin, Irfan ; Costa, Nadiesda ; Fatica, Richard ; Zaky, Ziad ; Gourishankar, Sita ; Poggio, Emilio ; Madill-Thomsen, Katelynn S ; Blosser, Christopher D ; Haler, Željka Veceric ; Budde, Klemens ; Halloran, Philip F ; Anand, Sanjiv ; Reeve, Jeff ; Miglinas, Marius ; Alhamad, Tarek ; Piecha, Grzegorz ; Naumnik, Beata ; Jurekovic, Zeljka ; Chow, Kevin ; Regele, Heinz ; Chamienia, Andrzej ; Bloudíčkova, Silvie Rajnochová ; Kant, Sam ; Kamel, Mahmoud
Emerging treatments for antibody-mediated rejection (ABMR, NEJM391 (2):122-132) have increased the importance of ABMR detection when donor-specific antibody (DSA) is negative. We addressed this issue in the Trifecta-Kidney study (ClinicalTrials.gov #NCT04239703) using 3 centralized tests in 690 kidney transplant biopsies: DSA (One Lambda Inc), blood donor-derived cell-free DNA (dd-cfDNA, Prospera™ test, Natera, Inc), and molecular biopsy assessment (MMDx). We used an "AutoBanff 2022" algorithm to model the impact of alternative DSA interpretations on the histologic diagnosis of DSA-negative ABMR following Banff guidelines, including agreement with dd-cfDNA and molecular ABMR. Lowering MFI cutoffs for DSA positivity did not improve the detection of DSA-negative ABMR. However, simply calling all DSA as positive allowed the Banff 2022 guidelines to identify 46% more ABMR cases with no measurable conventional DSA, and per net reclassification improvement increased agreement between histologic diagnoses and both dd-cfDNA (P = 7.72E-7) and molecular ABMR (P = 7.69E-7). New ABMR cases were as strongly positive for dd-cfDNA and molecular ABMR as those found using the conventional DSA interpretation. A validation set analysis using INTERCOMEX study data (ClinicalTrials.gov NCT#01299168) confirmed these findings and found that the new DSA-negative ABMR cases identified by calling all DSA-positive had the same risk for graft loss as those found with conventional DSA interpretation. Trifecta-Kidney Study ClinicalTrials.gov #NCT04239703.