Determinants of Poor Graft Outcome in Patients with Antibody-Mediated Acute Rejection

Lefaucheur, Carmen; Nochy, Dominique; Hill, Gary S.; Suberbielle-Boissel, Caroline; Antoine, Corinne; Charron, Dominique; Glotz, Denis

doi:10.1111/j.1600-6143.2006.01686.x

Cited by 141 publications

(107 citation statements)

References 47 publications

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“…Explaining "the Paradox" of Frequent Accommodation and Low Prevalence of Anti-HLA Antibodies Anti-HLA antibodies are generally considered detrimental for organ transplants, and the presence of these antibodies in the blood of a transplant recipient predicts rejection [17][18][19][20]. Consistent with this concept, anti-HLA antibodies are detected infrequently in those with normally functioning transplants.…”

Section: Accommodation In Clinical Transplantationsupporting

confidence: 54%

Accommodation of grafts: Implications for health and disease

Tang

Platt

2007

Human Immunology

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Accommodation refers to the acquired resistance of a graft to immune-mediated injury. It is typically observed after antibodies that would cause rejection of a graft are removed from a recipient and then return. Besides being a condition so induced, accommodation can occur spontaneously, without the depleting of antibodies. Indeed, we postulate that spontaneous accommodation may be the most common outcome of clinical organ transplantation. This communication will review the current understanding of accommodation, emphasizing recent advances and important questions. Among the recent advances are the discoveries of potentially broader relevance of accommodation for biology and immunology and pathways by which accommodation may be achieved. To investigate these pathways and to understand how accommodation begins and how it evolves, clinical organ transplants might offer a useful and incisive model.

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Section: Accommodation In Clinical Transplantationsupporting

confidence: 54%

Accommodation of grafts: Implications for health and disease

Tang

Platt

2007

Human Immunology

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“…In a 2007 study of biopsies for clinical rejection in confirmed AMR, we found v1 and v2 in 33.3 and 23.8% of patients at first biopsy, respectively. 22 Furthermore, we found that v1-v2 was closely correlated with signs of AMR (glomerulitis, PTC) and that the tubulitis expected with ACR was totally absent in 12/25 cases. We suggested on the basis of these findings that intimal vasculitis could be a manifestation of AMR rather than simply concomitant ACR.…”

Section: Relationship Of Arteriosclerosis To Vasculitic (V1 and V2) Lmentioning

confidence: 70%

Donor-Specific Antibodies Accelerate Arteriosclerosis after Kidney Transplantation

Hill

Nochy²,

Bruneval³

et al. 2011

Journal of the American Society of Nephrology

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In biopsies of renal allografts, arteriosclerosis is often more severe than expected based on the age of the donor, even without a history of rejection vasculitis. To determine whether preformed donor-specific antibodies (DSAs) may contribute to the severity of arteriosclerosis, we examined protocol biopsies from patients with (n ϭ 40) or without (n ϭ 59) DSA after excluding those with any evidence of vasculitis. Among DSA-positive patients, arteriosclerosis significantly progressed between month 3 and month 12 after transplant (mean Banff cv score 0.65 Ϯ 0.11 to 1.12 Ϯ 0.10, P ϭ 0.014); in contrast, among DSA-negative patients, we did not detect a statistically significant progression during the same timeframe (mean Banff cv score 0.65 Ϯ 0.11 to 0.81 Ϯ 0.10, P ϭ not significant). Available biopsies at later time points supported a rate of progression of arteriosclerosis in DSA-negative patients that was approximately one third that in DSA-positive patients. Accelerated arteriosclerosis was significantly associated with peritubular capillary leukocytic infiltration, glomerulitis, subclinical antibody-mediated rejection, and interstitial inflammation. In conclusion, these data support the hypothesis that donorspecific antibodies dramatically accelerate post-transplant progression of arteriosclerosis.

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“…Conventional assessment permits to diagnose ABMR but is insufficient for prediction of outcome and risk assessment in patients with ABMR. 17 Our hypothesis is that the ABMR Molecular Score and the endothelial transcripts reflect active remodeling of the microcirculation because of relatively recent antibody-mediated damage, implying the action of the antibody and its effector mechanism, and thus, can be used as a companion to the conventional features, such as histopathology. The ABMR Molecular Score is the weighted average of a larger set of genes selected using a simple t test comparing two classes of biopsies and then fine tuned using linear discriminant analysis, whereas the endothelial DSA-selective transcripts score is the unweighted average of a gene set selected using domainspecific knowledge of transplant biology.…”

Section: Discussionmentioning

confidence: 99%

Molecular Microscope Strategy to Improve Risk Stratification in Early Antibody-Mediated Kidney Allograft Rejection

Loupy

Lefaucheur

Vernerey

et al. 2014

Journal of the American Society of Nephrology

128

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Antibody-mediated rejection (ABMR) is the leading cause of kidney allograft loss. We investigated whether the addition of gene expression measurements to conventional methods could serve as a molecular microscope to identify kidneys with ABMR that are at high risk for failure. We studied 939 consecutive kidney recipients at Necker Hospital (2004-2010; principal cohort) and 321 kidney recipients at Saint Louis Hospital (2006-2010; validation cohort) and assessed patients with ABMR in the first 1 year post-transplant. In addition to conventional features, we assessed microarray-based gene expression in transplant biopsy specimens using relevant molecular measurements: the ABMR Molecular Score and endothelial donor-specific antibody-selective transcript set. The main outcomes were kidney transplant loss and progression to chronic transplant injury. We identified 74 patients with ABMR in the principal cohort and 54 patients with ABMR in the validation cohort. Conventional features independently associated with failure were donor age and humoral histologic score (g+ptc+v+cg+C4d). Adjusting for conventional features, ABMR Molecular Score (hazard ratio [HR], 2.22; 95% confidence interval [95% CI], 1.37 to 3.58; P=0.001) and endothelial donor-specific antibody-selective transcripts (HR, 3.02; 95% CI, 1.00 to 9.16; P,0.05) independently associated with an increased risk of graft loss. The results were replicated in the independent validation group. Adding a gene expression assessment to a traditional risk model improved the stratification of patients at risk for graft failure (continuous net reclassification improvement, 1.01; 95% CI, 0.57 to 1.46; P,0.001; integrated discrimination improvement, 0.16; P,0.001). Compared with conventional assessment, the addition of gene expression measurement in kidney transplants with ABMR improves stratification of patients at high risk for graft loss.

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Determinants of Poor Graft Outcome in Patients with Antibody-Mediated Acute Rejection

Cited by 141 publications

References 47 publications

Accommodation of grafts: Implications for health and disease

Accommodation of grafts: Implications for health and disease

Donor-Specific Antibodies Accelerate Arteriosclerosis after Kidney Transplantation

Molecular Microscope Strategy to Improve Risk Stratification in Early Antibody-Mediated Kidney Allograft Rejection

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