Dataset Information

Nanostring gene expression profiling in a mouse model of antibody-mediated rejection of kidney allografts

ABSTRACT: Acute and chronic antibody mediated rejection (ABMR) continues to decrease clinical kidney graft function and survival. Dysregulated donor-specific antibody (DSA) responses are induced in B6.CCR5-/- recipients of complete MHC-mismatched A/J kidney allografts with NK cells playing a critical role in the acute ABMR. We tested the role of neutrophils in ABMR by transplanting A/J kidneys to CCR5-/- mice with a deletion in the neutrophil serine protease cathepsin G. Whereas B6.CCR5-/- recipients rejected all kidney allografts between days 18-25, 70% of allografts survived beyond day 60 in B6.CCR5-/-cG-/- recipients. At days 15-17 post-transplant DSA titers in B6.CCR5-/-cG-/- recipients were 24.3-fold higher than those in wild-type C57BL/6 allograft recipients. Allografts from B6.CCR5-/-cG-/- recipients on days 45 and 60 had typical characteristics of chronic graft injury including interstitial collagen deposition and peri-glomerular fibrosis that was accompanied by a fibrogenic transcript signature and late post-transplant production of autoantibodies to many targets, including structural proteins including collagen IV and fibronectin. Depletion of B cells at the time DSA peak titers were achieved on day 14 post-transplant decreased serum autoantibodies levels, the kidney allograft fibrogenic transcript signature, and the chronic kidney allograft injury, despite maintenance of the high DSA titers. These results indicate a critical role for neutrophil cathepsin G during acute ABMR of kidney allografts and in its absence, DSA induced late appearance of autoantibodies mediating development of chronic kidney allograft injury.

ORGANISM(S): Mus musculus

PROVIDER: GSE301384 | GEO | 2026/07/06

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:We study the global gene expression profiles of TGP patients with or without graft loss to determine if a clinical and/or gene expression profile can predict allograft survival. Transplant glomerulopathy (TGP) carries a poor prognosis and is associated with decreased allograft survival. In a large series of kidney transplant recipients, graft loss was observed in 38% of TGP patients at 5 years compared to 5% in patients without TGP. Among patients with TGP, predictors of poor outcome included C4d deposition in the peritubular capillaries, higher serum creatinine and proteinuria at diagnosis, the severity of interstitial fibrosis, and GBM duplication (higher Banff M-bM-^@M-^Xchronic glomerulopathy [cg]M-bM-^@M-^Y score), and the presence of DSA. However, the importance of microvascular inflammation determined by peritubular capillaritis (ptc) and glomerulitis (g) scores and the strength of DSA has not been explored thoroughly. We have recently reported the intragraft gene expression profiles of TGP patients, with or without DSA. However, the association between gene expression profiles of biopsies and the allograft survival has not been investigated. In this study, in addition to known clinical and demographic factors associated with poor outcomes in TGP, we specifically aimed to investigate if intragraft gene expression profiles by microarrays, microvascular inflammation scores, and the strength of DSA determined by mean fluorescence intensity (MFI) values could predict allograft loss in TGP patients. The study population was derived from renal allograft biopsies diagnosed with TGP at Montefiore Medical Center, Bronx, NY from January 2009 to December 2012. All biopsies were clinically indicated for elevated creatinine or proteinuria. A retrospective chart review was conducted to record clinical, demographic, immunological, and histopathological parameters and graft outcomes. Graft loss was defined as requiring dialysis and/or retransplantation during follow-up. Of the 525 patients who underwent clinically indicated transplant kidney biopsies, 52 patients (10%) had diagnosis of TGP. Median follow up time after the biopsy was 23 months (range, 1-46). Seventeen patients (32%) lost their allografts (defined by return to dialysis or re-transplantation) at a median time of 16 months (range, 1-44). A subgroup of patients who were enrolled in the IRB-approved M-bM-^@M-^\Immune Monitoring StudyM-bM-^@M-^] and had clinically indicated biopsy samples were included in the analysis. A total of 28 biopsy samples (8 graft loss and 20 functioning allograft) were used for gene expression profiling.

Dataset Information

Nanostring gene expression profiling in a mouse model of antibody-mediated rejection of kidney allografts

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets