Banff 2019 Meeting Report: Molecular diagnostics in solid organ transplantation–Consensus for the Banff Human Organ Transplant (B-HOT) gene panel and open source multicenter validation

Abstract

This meeting report from the XV Banff conference describes the creation of a multiorgan 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 analyses, 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.

AKI and Collapsing Glomerulopathy Associated with COVID-19 and APOL 1 High-Risk Genotype

“…12 RNA was analyzed on an nCounter Max System (NanoString, Seattle. WA) using the 770 gene Human Organ Transplant Panel of probes 13 supplemented with the 10-gene probe COVID-19 Panel Plus Beta (NanoString). Eight probes are included for SARS-CoV-2 (envelope protein, membrane glycoprotein, nucleocapsid phosphoprotein, surface glycoprotein, and four open reading frames [orf1ab, 3a, 7a, and 8]).…”

Biomarker and surrogate development in vascularised composite allograft transplantation: Current progress and future challenges

“…A number of advanced biomarkers are now available for the detection of subclinical rejection of renal transplants and the in depth characterisation of tissue immune responses and damage, although many are still undergoing clinical validation. 11,12 Biomarkers currently exist that are common to all transplants and include (1) markers of the morbidity of immunosuppression e.g. hypertension, hyperlipidaemia, renal biochemistry, glucose function tests, white cell count (2) markers of immunosuppressive compliance and dosing e.g.…”

“…45 A number of probe-based assays now exist for in depth and technically straightforward assessment of tissue biopsy molecular markers based on consensus derived from robust microarray studies of SOT in the literature, although it is not yet clear whether these will also translate to skin biopsies. 12…”

Herausforderungen in der Behandlung später antikörpermediierter Abstoßung

“…Zusätzlich zu diesen Kriterien hat nun seit einigen Jahren auch zunehmend die Anwendung gut validierter molekularer Diagnostika wie das Molekulare Mikroskop (MMDx) oder die NanoString-Technologie an derzeit noch ausgewählten Zentren ihren Einzug in die Transplantationsmedizin gefunden und wurden auch bereits in die Banff-Klassifizierung aufgenommen [9,10]. Unter Zuhilfenahme dieser molekularen Methoden gelang es, die beiden morphologischen Haupttypen der ABMR, die aktive und die chronisch aktive ABMR, mittels spezieller "unsupervised" Algorithmen wie z.…”