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Down regulation of protective genes is associated with cellular and antibody‐mediated rejection
Author(s) -
LinWang Hui Tzu,
Cipullo Reginaldo,
Dinkhuysen Jarbas J.,
Finger Marco A.,
Rossi João M.,
Correia Edileide B.,
Hirata Mário H.
Publication year - 2017
Publication title -
clinical transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 76
eISSN - 1399-0012
pISSN - 0902-0063
DOI - 10.1111/ctr.13060
Subject(s) - medicine , immunohistochemistry , gene expression , transplantation , gene , heart transplantation , antibody , real time polymerase chain reaction , andrology , immunology , pathology , biology , genetics
Despite advances in immunosuppressive therapy, rejection still remains the main obstacle to a successful transplant. This study aims to explore the gene expression profile of the rejection process in order to decrease the number of unnecessary endomyocardial biopsies in stable patients. Methods A total of 300 formalin‐fixed and paraffin‐embedded ( FFPE ) endomyocardial biopsies sampled from 63 heart allograft recipients were included in this study. Acute cellular rejection ( ACR ) and antibody‐mediated rejection ( AMR ) were diagnosed by histological analysis and immunohistochemical C4d staining, respectively. Analysis of gene expression was performed by quantitative real‐time polymerase chain reaction. The samples were grouped according to the ISHLT rejection classification, aiming the statistical analysis. Results There was a significant decrease in the HMOX 1 , AIF 1, and CCL 2 transcript over the post‐transplantation period in non‐rejection group ( P <.001). Furthermore, the ADIPOR 1 , ADIPOR 2 , BCL 2L1, and VEGFA protective genes were significantly downregulated in the ACR group ( P <.05). ADIPOR 2, BCL 2L1, IL 6, and NOS 2 genes were also significantly downregulated in the AMR group than in the non‐rejection group ( P <.05). Conclusion The downregulations of the protective genes contribute to the allograft rejection, and the archived FFPE samples are useful for the gene expression analysis aiming the allograft rejection surveillance.