Impact of humoral alloreactivity early after transplantation on the long-term survival of renal allografts

Lederer, Stephan R.; Kluth-Pepper, B; Schneeberger, H.; Albert, E. D.; Land, W.; Feucht, Helmut E.

doi:10.1046/j.1523-1755.2001.00495.x

Cited by 157 publications

(140 citation statements)

References 24 publications

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“…Cosimi et al found that elevated ratios of helper T cells (CD4+) to CTLs (CD8+) were indicative of rejection (20) and Morton et al demonstrated that CD4+ cells are both necessary and sufficient to cause rejection in heart and skin allografts with MHC-class I mismatches (21). Humoral alloreactivity, which has been related to inferior graft outcome (22), offers an alternative or supporting mechanism of rejection initiation that cannot be detected with this assay.…”

Section: Discussionmentioning

confidence: 99%

Serial Peripheral Blood Perforin and Granzyme B Gene Expression Measurements for Prediction of Acute Rejection in Kidney Graft Recipients

Simon

Opelz

Wiesel

et al. 2003

American Journal of Transplantation

101

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In the present study we investigated whether peripheral blood gene expression measurements may serve as an early and non-invasive tool to predict renal allograft rejection. Peripheral blood was collected twice weekly after transplantation and gene expression was measured using real-time polymerase chain reaction (PCR). Recipients with acute rejection (n = 17) had higher levels of perforin and granzyme B transcript on days 5-7, 8-10, 11-13, 17-19, 20-22, and 26-29, as compared to patients without rejection (n = 50, p < 0.05 in all cases). Rejection diagnosis using gene expression criteria, determined with receiver operating characteristic (ROC) curves, was possible 2-30 days before traditional diagnosis (median 11 days). The best diagnostic result was obtained from samples taken on days 8-10, with a specificity of 90% and a sensitivity of 82% for perforin, and a specificity of 87% and sensitivity of 72% for granzyme B. Decreases in perforin (p < 0.01) and granzyme B expression (p < 0.05) were observed after initiation of anti-rejection therapy. Our data indicate that gene expression measurement is a useful tool for the recognition of graft rejection in its earliest stages. Serial measurements could be implemented as a monitoring system to highlight patients at higher risk of rejection, making them candidates for biopsy or pre-emptive anti-rejection therapy.

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Section: Discussionmentioning

confidence: 99%

Serial Peripheral Blood Perforin and Granzyme B Gene Expression Measurements for Prediction of Acute Rejection in Kidney Graft Recipients

Simon

Opelz

Wiesel

et al. 2003

American Journal of Transplantation

101

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“…We also experienced that EM of the glomeruli verified transplant glomerulopathy more precisely than did light microscopy (11). Pooled data indicate that acute rejection episodes or ongoing, subclinical rejection injuries to peritubular and glomerular capillary endothelial cells lead to the development of transplant capillaropathy and transplant glomerulopathy (11)(12)(13)(14)(15)(16). The cumulative incidence of peritubular and glomerular capillary lesions was 85%, suggesting that EM may be routinely used in the diagnosis of chronic rejection.…”

mentioning

confidence: 86%

“…Acute humoral rejection is characterized by the linear immunofluorescence of complement 4d along the capillary walls (16), and the necrosis of endothelial cells and denudation of the basement membrane observed on EM (22). The ultrastructural features of acute cellular rejection include hypertrophied endothelial cells, increased adherence and passage of lymphocytes, lymphocytes in the capillary wall, separation of endothelial cells from the basement membrane, defects in the endothelial lining and balloon-like fragmentation or apoptosis of endothelial cells in the vicinity of lymphocytes (12,23,24).…”

Section: Transplant Capillaropathymentioning

confidence: 99%

The Value of Electron Microscopy in the Diagnosis of Chronic Renal Allograft Rejection

et al. 2001

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The main causes of the late dysfunction of renal allografts are chronic rejection and chronic transplant nephropathy. Both are clinicopathologic entities, with a similar clinical presentation, but different histologic appearances. Chronic rejection is characterized by the presence of alloantigeninduced lesions (transplant arteriopathy and transplant glomerulopathy), and chronic transplant nephropathy by nonspecific sclerosing changes. The incidence of transplant arteriopathy and transplant glomerulopathy is relatively low. Electron microscopy (EM) may overcome the limitations in the histologic diagnosis of chronic rejection, because it verifies alloantigen-induced chronic microvasculopathy in the peritubular capillaries (transplant capillaropathy), and identifies transplant glomerulopathy more precisely than does light microscopy. To assess the value of EM in chronic rejection diagnosis, a retrospective search for transplant capillaropathy and transplant glomerulopathy was performed in a consecutive series of 91 biopsies performed >6 months after implantation (median: 26 months, range 6 -186) and the diagnoses were reclassified on the basis of the ultrastructural findings. The definitions used were: transplant capillaropathy: a peritubular capillary profile with seven or more circumferential basement membrane layers, or at least three profiles with five or six circumferential layers; ultrastructurally verified transplant glomerulopathy: thickening of the capillary wall in at least three loops in consequence of the widening of the subendothelial space by abnormal basement membrane material, and the formation of a new layer(s) of basal lamina; and chronic rejection: the presence of transplant capillaropathy and/or transplant glomerulopathy and/or transplant arteriopathy. Histologically, chronic transplant nephropathy, chronic rejection, chronic cyclosporine nephrotoxicity, glomerulonephritis, acute rejection, "suspicious" for acute rejection, and "others" were diagnosed in 37%, 34%, 21%, 19%, 57%, 30%, and 5% of the specimens, respectively. The results of EM increased the diagnosis of chronic rejection to 69% of the cases, and decreased chronic transplant nephropathy to 15%. The individual incidence of transplant capillaropathy and transplant glomerulopathy was 79% and 57%, respectively, and their cumulative incidence was 92%. Five biopsies exhibited merely transplant arteriopathy. A late dysfunction typically had more than one cause; the most frequent combination was chronic rejection and acute rejection. In conclusion, the EM search for transplant capillaropathy and transplant glomerulopathy doubled the frequency of the diagnosis of chronic rejection. Currently, the evaluation of renal allograft biopsies from recipients with a late dysfunction relies on standard light microscopy. Because light microscopy per se proved to be insensitive in the diagnosis of chronic rejection, incorporation of EM into the evaluation of late dysfunction biopsies is strongly recommended. The long-term survival of renal allografts is ...

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“…[1][2][3][4][5] C4d represents one criterion to the diagnosis of acute and chronic ABMR according to Banff classification. 6 Staining for C4d in peritubular capillaries is present in other histological diagnosis of kidney graft biopsies, such as acute cellular rejection and/or acute graft injury, 3 interstitial fibrosis and tubular atrophy, calcineurin inhibitor toxicity, and even in grafts without dysfunction and with no morphological signs of rejection.…”

Section: Introductionmentioning

confidence: 99%

Clinical and pathological correlations of C4d immunostaining and its infl uence on the outcome of kidney transplant recipients

Carpio¹,

Rech²,

Eickhoff³

et al. 2011

J. Bras. Nefrol.

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Impact of humoral alloreactivity early after transplantation on the long-term survival of renal allografts

Abstract: Humoral alloreactivity, manifested by the capillary deposition of complement C4d in about 50% of biopsied renal grafts, exerts a strong impact on graft survival when it operates within six months after transplantation.

Cited by 157 publications

References 24 publications

Serial Peripheral Blood Perforin and Granzyme B Gene Expression Measurements for Prediction of Acute Rejection in Kidney Graft Recipients

Serial Peripheral Blood Perforin and Granzyme B Gene Expression Measurements for Prediction of Acute Rejection in Kidney Graft Recipients

The Value of Electron Microscopy in the Diagnosis of Chronic Renal Allograft Rejection

Clinical and pathological correlations of C4d immunostaining and its infl uence on the outcome of kidney transplant recipients

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