An association between antibodies specific for endothelial cells and renal transplant failure

Perrey, Chris; Brenchley, Paul; Johnson, Raymond F.; Martin, Susan

doi:10.1016/s0966-3274(98)80024-5

Cited by 65 publications

(36 citation statements)

References 19 publications

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“…Positive C4d staining without concurrently detectable serum alloantibodies (which occurs in about 10% of human biopsies) might be due to non-HLA alloantibodies (47)(48)(49) ) or adsorption of antibodies by the graft. This study supports the later possibility because most of the alloantibody-negative, C4d-positive animals became alloantibody positive on subsequent testing or lost the C4d staining.…”

Section: Discussionmentioning

confidence: 99%

Four Stages and Lack of Stable Accommodation in Chronic Alloantibody Mediated Renal Allograft Rejection in Cynomolgus Monkeys

et al. 2008

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The etiology of immunologically mediated chronic renal allograft failure is unclear. One cause is thought to be alloantibodies. Previously in Cynomolgus monkeys, we observed a relationship among donor-specific alloantibodies (DSA), C4d staining, allograft glomerulopathy, allograft arteriopathy and progressive renal failure. To define the natural history of chronic antibody-mediated rejection and its effect on renal allograft survival, we now extend this report to include 417 specimens from 143 Cynomolgus monkeys with renal allografts. A subset of animals with long-term renal allografts made DSA (48%), were C4d positive (29%), developed transplant glomerulopathy (TG) (22%) and chronic allograft arteriopathy (CAA) (19%). These four features were highly correlated and associated with statistically significant shortened allograft survival. Acute cellular rejection, either Banff type 1 or 2, did not correlate with alloantibodies, C4d deposition or TG. However, endarteritis (Banff type 2) correlated with later CAA. Sequential analysis identified four progressive stages of chronic antibody-mediated rejection: (1) DSA, (2) deposition of C4d, (3) TG and (4) rising creatinine/ renal failure. These new findings provide strong evidence that chronic antibody-mediated rejection develops without enduring stable accommodation, progresses through four defined clinical pathological stages and shortens renal allograft survival.

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Section: Discussionmentioning

confidence: 99%

Four Stages and Lack of Stable Accommodation in Chronic Alloantibody Mediated Renal Allograft Rejection in Cynomolgus Monkeys

et al. 2008

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“…Anti-endothelium/monocyte antibodies have been shown to be associated with hyperacute rejection, although this is probably rare (33). Two previous studies showed higher anti-endothelial cell antibodies in patients with a failed renal transplant as a result of chronic rejection compared with patients with functioning allografts (34,35). A recent intriguing study also revealed antibodies targeting angiotensin II type 1 receptor in kidney transplant recipients with "vascular rejection," who did not have detectable DS anti-HLA antibodies (36).…”

Section: Type Of Antibody and Its Effect On Allograft Outcomementioning

confidence: 99%

Sensitization after Kidney Transplantation

Akalin¹,

Pascual²

2006

Clinical Journal of the American Society of Nephrology

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Kidney transplant recipients may develop de novo anti-HLA and non-HLA antibodies after transplantation. Although these antibodies may be donor-specific or non-donor-specific, their presence may increase the risk for acute and chronic rejection, thereby decreasing allograft survival. The introduction of more sensitive and specific methods to detect anti-HLA antibodies, such as Flow Specific Beads and FlowPRA, both before and after transplantation, will help to define immunologically high-risk kidney transplant recipients. Thus, posttransplantation monitoring of anti-HLA antibody production will allow the identification of kidney transplant recipients who might be at increased risk for late allograft failure. Moreover, knowledge of alloantibody status after transplantation may help to guide the appropriate use of immunomodulatory agents to downregulate anti-HLA antibody production.

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“…The presence of AECA has been previously reported in HLAidentical kidney transplants, indicating that AECA might be associated with transplant rejection (5,6). AECA can cause hyperacute rejection (HAR) and immediate graft loss (7)(8)(9)(10)(11). In the revised Banff criteria of 2001, it is believed that AECA can cause AMR in addition to antibodies to donor HLA (12).…”

mentioning

confidence: 99%

Circulating Anti-endothelial Cell Antibodies Are Associated with Poor Outcome in Renal Allograft Recipients with Acute Rejection

Sun¹,

Liu²,

Chen³

et al. 2008

Clinical Journal of the American Society of Nephrology

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Background and objectives: Anti-endothelial cell antibody (AECA) can cause hyperacute rejection and immediate graft loss after renal transplantation; however, its prevalence and significance during acute rejection are unknown. Previous studies suggested that AECA may be detected in recipients with acute vascular rejection (AVR).Design, setting, participants, & measurements: We retrospectively analyzed 653 cadaveric renal transplant recipients; circulating AECA was positive in 13 of 47 cases of AVR; another two cases of hyperacute rejection also had detectable AECA. Twenty-six cases of AVR without circulating AECA were selected as controls.Results: AECA-positive AVR usually occurred within 1 yr after transplantation and mostly was resistant to steroid treatment. Compared with the control group, the AECA-positive group was associated with a significantly lower 1-yr graft survival rate (46.7 versus 80.5%; P ‫؍‬ 0.038), and more patients had histologic interstitial plasma cell infiltration (53.8 versus 11.5%; P ‫؍‬ 0.005). More patients with AECA-positive AVR experienced another one or more episodes of acute rejection during 1 yr of follow-up (75.0 versus 13.0%; P ‫؍‬ 0.003). AECA-positive AVR with C4d deposition in peri-tubular capillaries had the worst outcome in this cohort, and it accounted for 38.5% graft loss in AVR. AECA in turn accounted for 71.4% of graft loss in C4d ؉ AVR.

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An association between antibodies specific for endothelial cells and renal transplant failure

Cited by 65 publications

References 19 publications

Four Stages and Lack of Stable Accommodation in Chronic Alloantibody Mediated Renal Allograft Rejection in Cynomolgus Monkeys

Four Stages and Lack of Stable Accommodation in Chronic Alloantibody Mediated Renal Allograft Rejection in Cynomolgus Monkeys

Sensitization after Kidney Transplantation

Circulating Anti-endothelial Cell Antibodies Are Associated with Poor Outcome in Renal Allograft Recipients with Acute Rejection

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