Hyperacute Rejection of Kidney Allografts, Associated With Pre-Existing Humoral Antibodies Against Donor Cells

Kissmeyer-Nielsen, F; Olsen, Steen; Petersen, V. Posborg; Fjeldborg, O

doi:10.1016/s0140-6736(66)92829-7

Cited by 762 publications

(162 citation statements)

References 6 publications

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“…Lymphocytotoxic antibodies (18)(19)(20)(21) and possibly reticuloendothelial-specific (22) antibodies have also been shown to have similar effects. The target of destruction is the kidney microvasculature, which is ruined and plugged with thrombi so quickly that the descriptive term hyperacute rejection has been applied.…”

Section: Discussionmentioning

confidence: 99%

A clinicopathological study of human liver allograft recipients harboring preformed IgG lymphocytotoxic antibodies

et al. 1992

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Twenty-six adult patients with preformed IgG donor lymphocytotoxic antibodies received primary liver allografts under FK 506 immunosuppression. The effect of the crossmatch-positive state on early graft function and on the immunopathological and histo-pathological findings was compared with that of 52 crossmatch-negative control recipients. The presensitized (Crossmatch-positive) patients had prolongation of early graft dysfunction, underwent more clinically indicated biopsies and had a higher incidence of cellular rejection, both overall (p < 0.05) and within 10 days of transplantation (p < 0.01). They also had a higher incidence of graft failure in the first 180 days (p < 0.01). Hyperacute rejection with necrotizing or neutrophilic arteritis was not seen in the crossmatchpositive grafts. However, histological findings associated with presensitization included platelet margination in central veins and sinusoids in biopsy specimens 60 to 90 min after graft revascularization. Later biopsy specimens had neutrophilic portal venulitis followed by cholangiolar proliferation, acute cholangiolitis and centrilobular hepatocyte swelling that mimicked preservation injury, endothelial activation of arteries with medial changes and relapsing episodes of acute cellular rejection. These clinicopathological observations suggest that lymphocytotoxic antibodies can have a deleterious effect on liver allograft function and survival, even if they do not precipitate immediate or hyperacute rejection. (Hepatology 1992;16:671-681.) Although the liver is known to be more resistant than other solid organs to injury from preformed graft antibodies in the recipient (1-3), this privileged state is not absolute (4,5). Identification of the consequences of humoral antibody states on the liver has been hampered by the lack of distinctive pathological findings in many cases in which humoral rejection was suspected but was not proved. Consequently, in this study of liver recipients with preformed donor lymphocytotoxic antibodies, we have attempted to determine whether a unique, pathologically identifiable form of graft injury could be recognized and whether pathophysiological mechanisms of liver allograft injury could be deduced. A similar study on the pathological nature of ABO-mismatched livers in which the graft antibodies were isoagglutinins was published recently (6). MATERIALS AND METHODS Patient SelectionDuring the 11-mo period between November 31, 1989, and September 9, 1990, 243 adult patients ( > 16 yr) were given primary liver allografts under FK 506 and low-dose steroid therapy. The sera of 26 (11%) contained donor lymphocytotoxic antibodies. The crossmatchnegative control patients (n = 52) were those treated just before and after the crossmatchpositive cases. Most of these same cases were part of a recent clinical report (5). There were no statistically significant differences between the two cohorts with respect to age, United Network of Organ Sharing urgency of need status, original disease, donor demographic data or...

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Section: Discussionmentioning

confidence: 99%

A clinicopathological study of human liver allograft recipients harboring preformed IgG lymphocytotoxic antibodies

et al. 1992

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“…Although detrimental roles of antibodies were first recognized in late 1960s, the link to graft pathology remained unrecognized for decades (1,2). In the early 1990s, clinicopathologic observations led to the recognition of histopathological features of acute ABMR in kidney (3,4), followed by discovery of C4d staining (5 (8,9) or noncomplement activating DSA (10)(11)(12) (27) (32).…”

Section: Abmr: An Underestimated Problem In Allografts Robert Colvin mentioning

confidence: 99%

Banff ’09 Meeting Report: Antibody Mediated Graft Deterioration and Implementation of Banff Working Groups

Sis

Mengel

Haas

et al. 2010

American Journal of Transplantation

697

586

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The 10th Banff Conference on Allograft Pathology was held in Banff, Canada from August 9 to 14, 2009. A total of 263 transplant clinicians, pathologists, surgeons, immunologists and researchers discussed several aspects of solid organ transplants with a special focus on antibody mediated graft injury. The willingness of the Banff process to adapt continuously in response to new research and improve potential weaknesses, led to the implementation of six working groups on the following areas: isolated v-lesion, fibrosis scoring, glomerular lesions, molecular pathology, polyomavirus nephropathy and quality assurance. Banff working groups will conduct multicenter trials to evaluate the clinical relevance, practical feasibility and reproducibility of potential changes to the Banff classification. There were also sessions on quality improvement in biopsy reading and utilization of virtual microscopy for maintaining competence in transplant biopsy interpretation. In addition, compelling molecular research data led to the discussion of incorporation of omics-technologies and discovery of new tissue markers with the goal of combining histopathology and molecular parameters within the Banff working classification in the near future.

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“…Heparan sulfate proteoglycan also renders endothelial surfaces relatively impermeable to transit of blood cells and plasma proteins (3,4). Intravascular coagulation and extravasation of blood elements are prominent pathological features of hyperacute rejection (5) and other diseases thought to be mediated by the binding of antibodies to endothelium and the consequent activation of complement. We therefore used an in vitro model to test the hypothesis that binding of human natural antibodies to xenogeneic endothelium might lead to a change in cell-associated proteoglycan, which in turn might eventuate the pathological picture of hyperacute rejection (6)(7)(8)(9)(10)(11).…”

mentioning

confidence: 99%

Release of heparan sulfate from endothelial cells. Implications for pathogenesis of hyperacute rejection.

Platt

Vercellotti

Lindman

et al. 1990

The Journal of Experimental Medicine

252

119

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Heparan sulfate proteoglycan associated with endothelial cells in normal blood vessels inhibits intravascular coagulation and egress of blood cells and plasma proteins, key features of hyperacute rejection. It was shown herein that exposure of cultured porcine endothelium to human serum as a source of natural antibodies and complement caused cleavage and release of 5% of endothelial cell proteoglycans within 4 min and greater than 50% within 1 h. Proteoglycan release depended on activation of the classical complement pathway and preceded irreversible cell injury. These findings suggest that loss of endothelial cell proteoglycan may be a critical step in the pathogenesis of hyperacute rejection and in diseases involving humoral injury to endothelial cells.

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Hyperacute Rejection of Kidney Allografts, Associated With Pre-Existing Humoral Antibodies Against Donor Cells

Cited by 762 publications

References 6 publications

A clinicopathological study of human liver allograft recipients harboring preformed IgG lymphocytotoxic antibodies

A clinicopathological study of human liver allograft recipients harboring preformed IgG lymphocytotoxic antibodies

Banff ’09 Meeting Report: Antibody Mediated Graft Deterioration and Implementation of Banff Working Groups

Release of heparan sulfate from endothelial cells. Implications for pathogenesis of hyperacute rejection.

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