RNA Expression Profiling of Renal Allografts in a Non-Human Primate Identifies Inflammation as a Risk Factor in Chronic Antibody Mediated Rejection
1Pathology, Massachusetts General Hospital, Boston, MA
2Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada
3Surgery, Massachusetts General Hospital, Boston, MA.
Meeting: 2018 American Transplant Congress
Abstract number: C28
Keywords: Alloantibodies, Bone marrow transplantation, Kidney transplantation, Rejection
Session Information
Session Name: Poster Session C: Kidney Chronic Antibody Mediated Rejection
Session Type: Poster Session
Date: Monday, June 4, 2018
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall 4EF
Introduction
Chronic alloantibody mediated rejection (CAMR) is a major risk factor in renal allografts. Some inflammation is commonly identified within CAMR, though mostly low grade, and is not commonly diagnosed. Some investigators deem these mixed rejections. This abstract tests the hypothesis that inflammation within CAMR adversely affects renal allograft survival.
Methods
Included were 76 animals from a BMT model with one to 11 biopsies (zero to 5983 days post-transplantation, n = 278). Samples included protocol, indication, and autopsy nephrectomies from normals, and various grades of ACR and CHR. The gene set includes 67 oligonucleotides derived from human studies. JMP13 programs included Fit Model (scaled estimates), K-Means clustering, Factor Analysis. All p values were adjusted for false discovery. Factor analysis was chosen to reduce the many numerated gene expressions into smaller sets of correlated variables
Results
To explore RNA expression in CAMR three factors derived solely from T cell and interferon, endothelial and NK genes (Eigen values >4) were clustered into nine clusters (K-Means). Three of the nine clusters showed marked elevation of endothelial genes and inflammatory genes and deemed mixed rejections. One cluster contained only elevated endothelial genes (pure CAMR). The other clusters are normal and TCMR. The mixed clusters included TCMR Banff grades of inflammation (> borderline). The pure CAMR was pathologically no TCMR. The median survival of the pure CAMR was longer than the three mixed groups. The median survival of the mixed were not different. These results were confirmed by Proportional Hazard risk ratio for the pure CAMR group as compared to the mixed groups, P<0.02. 
Conclusions
These findings suggest that inflammation within CAMR (mixed rejections) is an additional risk for shortened allograft survival.
CITATION INFORMATION: Smith R., Adam B., Rosales A., Matsunami M., Oura T., Cosimi B., Kawai T., Mengel M., Colviin R. RNA Expression Profiling of Renal Allografts in a Non-Human Primate Identifies Inflammation as a Risk Factor in Chronic Antibody Mediated Rejection Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Smith R, Adam B, Rosales A, Matsunami M, Oura T, Cosimi B, Kawai T, Mengel M, Colviin R. RNA Expression Profiling of Renal Allografts in a Non-Human Primate Identifies Inflammation as a Risk Factor in Chronic Antibody Mediated Rejection [abstract]. https://atcmeetingabstracts.com/abstract/rna-expression-profiling-of-renal-allografts-in-a-non-human-primate-identifies-inflammation-as-a-risk-factor-in-chronic-antibody-mediated-rejection/. Accessed November 23, 2024.« Back to 2018 American Transplant Congress