Intragraft Gene Expression in Positive Crossmatch Kidney Allografts: Ongoing Inflammation Mediates Chronic Antibody-Mediated Injury

被引：43

作者：

Dean, P. G. ^{[1
]}

Park, W. D. ^{[1
]}

Cornell, L. D. ^{[2
]}

Gloor, J. M. ^{[3
]}

Stegall, M. D. ^{[1
]}

机构：

[1] Mayo Clin, Coll Med, Div Transplantat Surg, Dept Surg, Rochester, MN 55905 USA

[2] Mayo Clin, Coll Med, Div Anat Pathol, Dept Lab Med & Pathol, Rochester, MN USA

[3] Mayo Clin, Coll Med, Div Nephrol & Hypertens, Dept Med, Rochester, MN USA

来源：

AMERICAN JOURNAL OF TRANSPLANTATION | 2012年 / 12卷 / 06期

关键词：

Accommodation; anti-HLA antibody; kidney transplant; transplant glomerulopathy; DONOR-SPECIFIC ANTIBODY; TRANSPLANT GLOMERULOPATHY; LIVING-DONOR; HUMORAL REJECTION; ACCOMMODATION; RECIPIENTS; DESENSITIZATION; PLASMAPHERESIS; PROTOCOL; ALLOWS;

D O I：

10.1111/j.1600-6143.2011.03964.x

中图分类号：

R61 [外科手术学];

学科分类号：

摘要：

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.

引用

页码：1551 / 1563

页数：13

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