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Intragraft Gene Expression in Positive Crossmatch Kidney Allografts: Ongoing Inflammation Mediates Chronic Antibody‐Mediated Injury
Author(s) -
Dean P. G.,
Park W. D.,
Cornell L. D.,
Gloor J. M.,
Stegall M. D.
Publication year - 2012
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2011.03964.x
Subject(s) - medicine , gene expression , gene , inflammation , kidney , microarray , immune system , antibody , kidney transplantation , immunohistochemistry , immunology , microarray analysis techniques , fold change , pathology , biology , genetics
We studied intragraft gene expression profiles of positive crossmatch (+XM) kidney transplant recipients who develop transplant glomerulopathy (TG) and those who do not. Whole genome microarray analysis and quantitative rt‐PCR were performed on RNA from protocol renal allograft biopsies in three groups: (1) +XM/TG+ biopsies before and after TG; (2) +XM/NoTG; and (3) negative crossmatch kidney transplants (control). Microarray comparisons showed few differentially expressed genes between paired biopsies from +XM/TG+ recipients before and after the diagnosis of TG. Comparing +XM/TG+ and control groups, significantly altered expression was seen for 2447 genes (18%) and 3200 genes (24%) at early and late time points, respectively. Canonical pathway analyses of differentially expressed genes showed inflammatory genes associated with innate and adaptive immune responses. Comparing +XM/TG+ and +XM/NoTG groups, 3718 probe sets were differentially expressed but these were over‐represented in only four pathways. A classic accommodation phenotype was not identified. Using rt‐PCR, the expression of inflammatory genes was significantly increased in +XM/TG+ recipients compared to the +XM/NoTG and control groups. In conclusion, pretransplant donor‐specific anti‐HLA antibodies results in a gene expression profile characterized by inflammation and cellular infiltration and the majority of +XM grafts are exposed to chronic injury.