The lack of appropriate in situ biomarkers available to detect acute rejection makes it difficult to optimize anti-rejection therapies for heterogeneous forms of alloreactive processes in transplant recipients. To assess variations of genetic subtypes with morphologically similar histological patterns, as well as discrimination between types of rejection and other processes, we studied alterations in gene expression in renal allograft FFPE biopsy samples. Sixty-eight renal formalin-fixed paraffin-embedded biopsies were analyzed by RT-PCR using microfluidic cards containing 600 human signatures for immune, inflammatory and apoptosis genes. More than 150 transcripts showed significantly increased expression with acute cellular rejection (ACR), acute antibody mediated rejection (AAMR) or mixed rejection (ACR + AAMR), compared to normal donor biopsies (N) and non-rejecting (NR) cases. Forty-seven of these discovery phase immune, inflammation and apoptosis genes were selected to create a custom validation microfluidic card array tested on 150 new FFPE renal transplant biopsies. As the grade of ACR and AAMR rejection intensified, there was a marked increase in the sensitivity and specificity (80%, 90% respectively) for ACR/AAMR/Mixed Rejection using NR samples as cut-offs; initial analysis indicates distinct profiles between the different types of acute rejection. Banff Borderline category biopsies showed the lowest significantly different gene upregulation but also genetic subtypes. Non-rejection inflammatory conditions showed some gene upregulation but initial evaluation revealed different profiles from rejection. Our data reveals that FFPE biopsies serve as valid gene profiling sources for renal transplants with the expression level of certain genes correlating with inflammatory intensity and type of intragraft alloimmune process. Moreover, morphologically similar histological patterns contain diverse immune/inflammatory/apoptosis gene profiles, implying distinct potential for progress to graft injury or non-injurious phenotype. The genes validated in this study allow further refinement of morphologically based biopsy interpretation and help define more precise antirejection therapy.
To cite this abstract in AMA style:Ruiz P, Margolles-Clark E, Sageshima J, Ciancio G, Chen L, Mattiazi A, Guerra G, Kupin W, Roth D, Burke G. Immune, Inflammatory and Apoptosis Gene Expression in Human Formalin-Fixed Paraffin-Embedded (FFPE) Kidney Biopsies Correlate with Banff Scored Acute Rejection and Reveals Heterogeneous Genetic Subtypes Bearing Common Histological Patterns [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/immune-inflammatory-and-apoptosis-gene-expression-in-human-formalin-fixed-paraffin-embedded-ffpe-kidney-biopsies-correlate-with-banff-scored-acute-rejection-and-reveals-heterogeneous-genetic-subtyp/. Accessed December 5, 2020.
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