Donor-specific antibody is associated with increased expression of rejection transcripts in renal transplant biopsies classified as no rejection

Katelynn S. Madill-Thomsen, Georg A. Böhmig, Jonathan Bromberg, Gunilla Einecke, Farsad Eskandary, Gaurav Gupta, Luis G. Hidalgo, Marek Myslak, Ondrej Viklicky, Agnieszka Perkowska-Ptasinska, Philip F. Halloran, Roslyn Mannon, Daniel Serón, Joana Sellarés, Enver Akalin, Declan de Freitas, Michael Picton, Matt Weir, Klemens Budde, Timm HeinbokelHarold Yang, Seth Narins, Milagros Samaniego-Picota, Carmen Lefaucheur, Alexandre Loupy, Adam Bingaman, Daniel Brennan, Andrew Malone, Bertram Kasiske, Arthur Matas, Arjang Djamali

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Background Donor -specific HLA antibody (DSA) is present in many kidney transplant patients whose biopsies are classified as no rejection (NR). We explored whether in some NR kidneys DSA has subtle effects not currently being recognized. Methods We used microarrays to examine the relationship between standard-of-care DSA and rejection-related transcript increases in 1679 kidney transplant indication biopsies in the INTERCOMEX study ( NCT01299168), focusing on biopsies classified as NR by automatically assigned archetypal clustering. DSA testing results were available for 835 NR biopsies and were positive in 271 (32%). Results DSA positivity in NR biopsies was associated with mildly increased expression of antibody-mediated rejection (ABMR)-related transcripts, particularly IFNG-inducible and NK cell transcripts. We developed a machine learning DSA probability (DSAProb) classifier based on transcript expression in biopsies from DSA-positive versus DSA-negative patients, assigning scores using 10-fold cross-validation. This DSAProb classifier was very similar to a previously described “ABMR probability” classifier trained on histologic ABMR in transcript associations and prediction of molecular or histologic ABMR. Plotting the biopsies using Uniform Manifold Approximation and Projection revealed a gradient of increasing molecular ABMR-like transcript expression in NR biopsies, associated with increased DSA (P
Original languageEnglish (US)
Pages (from-to)2743-2758
Number of pages16
JournalJournal of the American Society of Nephrology
Issue number11
StatePublished - Nov 1 2021


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