The XV. Banff conference for allograft pathology was held in conjunction with the annual meeting of the American Society for Histocompatibility and Immunogenetics in Pittsburgh, PA (USA) and focused on refining recent updates to the classification, advances from the Banff working groups, and standardization of molecular diagnostics. This report on kidney transplant pathology details clarifications and refinements to the criteria for chronic active (CA) T cell–mediated rejection (TCMR), borderline, and antibody‐mediated rejection (ABMR). The main focus of kidney sessions was on how to address biopsies meeting criteria for CA TCMR plus borderline or acute TCMR. Recent studies on the clinical impact of borderline infiltrates were also presented to clarify whether the threshold for interstitial inflammation in diagnosis of borderline should be i0 or i1. Sessions on ABMR focused on biopsies showing microvascular inflammation in the absence of C4d staining or detectable donor‐specific antibodies; the potential value of molecular diagnostics in such cases and recommendations for use of the latter in the setting of solid organ transplantation are presented in the accompanying meeting report. Finally, several speakers discussed the capabilities of artificial intelligence and the potential for use of machine learning algorithms in diagnosis and personalized therapeutics in solid organ transplantation.

The 11th Banff meeting was held in Paris, France, from June 5 to 10, 2011, with a focus on refining diagnostic criteria for antibody‐mediated rejection (ABMR). The major outcome was the acknowledgment of C4d‐negative ABMR in kidney transplants. Diagnostic criteria for ABMR have also been revisited in other types of transplants. It was recognized that ABMR is associated with heterogeneous phenotypes even within the same type of transplant. This highlights the necessity of further refining the respective diagnostic criteria, and is of particular significance for the design of randomized clinical trials. A reliable phenotyping will allow for definition of robust end‐points. To address this unmet need and to allow for an evidence‐based refinement of the Banff classification, Banff Working Groups presented multicenter data regarding the reproducibility of features relevant to the diagnosis of ABMR. However, the consensus was that more data are necessary and further Banff Working Group activities were initiated. A new Banff working group was created to define diagnostic criteria for ABMR in kidneys independent of C4d. Results are expected to be presented at the 12th Banff meeting to be held in 2013 in Brazil. No change to the Banff classification occurred in 2011.

The XVI-th Banff Meeting for Allograft Pathology was held in Banff, Alberta, Canada, from 19th-23rd September 2022, as a joint meeting with the Canadian Society of Transplantation. To mark the 30^th anniversary of the first Banff Classification, pre-meeting discussions were held on the past, present, and future of the Banff Classification. This report is a summary of the meeting highlights that were most important in terms of their effect on the Classification, including discussions around microvascular inflammation and biopsy-based transcript analysis for diagnosis. In a post-meeting survey, agreement was reached on the delineation of the following phenotypes: (1) "Probable antibody-mediated rejection (AMR)", which represents DSA-positive cases with some histological features of AMR but below current thresholds for a definitive AMR diagnosis; and (2) "Microvascular inflammation (MVI), DSA-negative and C4d-negative", a phenotype of unclear cause requiring further study, which represents cases with MVI not explained by DSA. Although biopsy-based transcript diagnostics are considered promising and remain an integral part of the Banff Classification (limited to diagnosis of AMR), further work needs to be done to agree on the exact classifiers, thresholds, and clinical context of use.

This Meeting Report from the XV^th Banff conference describes the creation of a multi‐organ transplant gene panel by the Banff Molecular Diagnostics Working Group (MDWG). This Banff Human Organ Transplant (B‐HOT) panel is the culmination of previous work by the MDWG to identify a broadly useful gene panel based on whole transcriptome technology. A data driven process distilled a gene list from peer reviewed comprehensive microarray studies that discovered and validated their use in kidney, liver, heart and lung transplant biopsies. These were supplemented by genes that define relevant cellular pathways and cell types plus 12 reference genes used for normalization. The 770 gene B‐HOT panel includes the most pertinent genes related to rejection, tolerance, viral infections, and innate and adaptive immune responses. This commercially available panel uses the NanoString platform, which can quantitate transcripts from formalin fixed paraffin embedded samples. The B‐HOT panel will facilitate multicenter collaborative clinical research using archival samples and permit the development of an open source large database of standardized analyzes, thereby expediting clinical validation studies. The MDWG believes that a pathogenesis and pathway based molecular approach will be valuable for investigators and promote therapeutic decision‐making and clinical trials.

Emerging molecular analysis can be used as an objective and independent assessment of histopathological scoring systems. We compared the existing Banff i‐score to the total inflammation (total i‐) score for assessing the molecular phenotype in 129 renal allograft biopsies for cause. The total i‐score showed stronger correlations with microarray‐based gene sets representing major biological processes during allograft rejection. Receiver operating characteristic curves showed that total‐i was superior (areas under the curves 0.85 vs. 0.73 for Banff i‐score, p = 0.012) at assessing an abnormal cytotoxic T‐cell burden, because it identified molecular disturbances in biopsies with advanced scarring. The total‐i score was also a better predictor of graft survival than the Banff i‐score and essentially all current diagnostic Banff categories. The exception was antibody‐mediated rejection which is able to predict graft loss with greater specificity (96%) but at low sensitivity (38%) due to the fact that it only applies to cases with this diagnosis. The total i‐score is able to achieve moderate sensitivities (60–80%) with losses in specificity (60–80%) across the whole population. Thus, the total i‐score is superior to the current Banff i‐score and most diagnostic Banff categories in predicting outcome and assessing the molecular phenotype of renal allografts.

The purpose of the STAR 2019 Working Group was to build on findings from the initial STAR report to further clarify the expectations, limitations, perceptions, and utility of alloimmune assays that are currently in use or in development for risk assessment in the setting of organ transplantation. The goal was to determine the precision and clinical feasibility/utility of such assays in evaluating both memory and primary alloimmune risks. The process included a critical review of biologically driven, state of the art, clinical diagnostics literature by experts in the field, and an open public forum in a face‐to‐face meeting to promote broader engagement of the AST and ASHI membership. This report summarizes the literature review and the workshop discussions. Specifically, it highlights: (i) available assays to evaluate the attributes of HLA antibodies, and their utility both as clinical diagnostics and as research tools to evaluate the effector mechanisms driving rejection; (ii) potential assays to assess the presence of alloimmune T‐ and B‐cell memory; and (iii) progress in the development of HLA molecular mismatch computational scores as a potential prognostic biomarker for primary alloimmunity and its application in research trial design.