Non–Human Leukocyte Antigen Antibodies Reactive with Endothelial Cells Could Be Involved in Early Loss of Renal Allografts

Ronda, C; Borba, Susan C. P.; Ferreira, Simone Aparecida; Glotz, Denis; Ianhez, Luiz Estevam; Rodrigues, H.; Viggiani, C.; Nahas, Willian; David‐Neto, Elias; Castro, Maria Cristina Ribeiro de; Daisa, S.R. David; Kalil, Jorge; Panajotopoulos, N

doi:10.1016/j.transproceed.2011.03.059

Cited by 12 publications

(15 citation statements)

References 10 publications

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“…Similar to the report by Ronda et al, biopsies from all three rejected kidney allografts from our patient showed no evidence of complement activation as measured by C4d immunofluorescence (12). The absence of complement involvement was also supported by the fact that early administration on POD 1 of eculizumab, a complement component C5 inhibitor, was ineffective in controlling the antibody‐mediated damage (13).…”

Section: Discussionsupporting

confidence: 91%

“…AECAs were detected in the sera of seven renal transplant recipients with early graft losses who cumulatively had lost 20 allografts, five of which were HLA identical (2). Finally, a recent collaborative study by Ronda et al evaluated 11 renal recipients with early graft loss due to humoral rejection; all had detectable AECAs but no evidence of HLA‐DSA or complement activation as measured by C4d (12). Our case study substantiates the findings of these earlier studies because we have ruled out the presence of HLA‐DSA, including antibodies specific for HLA‐DQ and HLA‐DP, through the use of sensitive bead immunoassays.…”

Section: Discussionmentioning

confidence: 99%

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Multiple Hyperacute Rejections in the Absence of Detectable Complement Activation in a Patient With Endothelial Cell Reactive Antibody

Jackson¹,

Kuperman²,

Montgomery³

2012

American Journal of Transplantation

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This case involves a 54-year-old patient with polycystic kidney disease and a history of hyperacute allograft rejections. Two previous compatible live donor transplants functioned immediately but failed within the first 12 h due to antibody-injury. This patient was referred for a third transplant due to decreased vascular access and progressive hypotension from uremic autonomic dysfunction. He was broadly sensitized to HLA; however, a live donor was identified through kidney paired donation for whom he had no donor-specific HLA antibody (HLA-DSA). This patient received one plasmapheresis (PP) and intravenous immunoglobulin (IVIg) treatment, anti-CD25, and anti-CD20 antibodies prior to transplant. The allograft functioned immediately but became anuric within 24 h. A biopsy revealed antibody-mediated injury in the absence of C4d. Daily PP/IVIg, a second dose of anti-CD20, and eculizumab were administered. A retrospective endothelial cell crossmatch (ECXM) was positive with serum drawn 3 days prior to transplant and these EC antibodies were enriched for IgG2 and IgG4, noncomplement activating subclasses. Postoperative day (POD) 3, HLA-DSA remained negative but a rescue splenectomy was performed. Cultured splenocytes produced antibodies that bound donor ECs but not lymphocytes. Bortezomib was initiated on POD5. Despite aggressive therapy, the allograft never regained function.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Multiple Hyperacute Rejections in the Absence of Detectable Complement Activation in a Patient With Endothelial Cell Reactive Antibody

Jackson¹,

Kuperman²,

Montgomery³

2012

American Journal of Transplantation

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“…Over the years, greater recognition of the role of antiendothelial cell antibodies (AECAs) in renal transplantation has provided researchers with an additional parameter to account for unexplained allograft losses. Several investigators have reported a significant correlation between the development of AECAs and hyperacute, accelerated, and acute renal rejections, even in situations involving HLA‐identical sibling transplants . The potential antigenic targets of AECAs that have been implicated with renal allograft rejection include angiotensin II type 1 receptor, vimentin, agrin (glomerular basement protein), and MICA .…”

Section: Immunobiology Of Transplantationmentioning

confidence: 99%

“…Several investigators have reported a significant correlation between the development of AECAs and hyperacute, accelerated, and acute renal rejections, even in situations involving HLA-identical sibling transplants. [70][71][72][73][74][75] The potential antigenic targets of AECAs that have been implicated with renal allograft rejection include angiotensin II type 1 receptor, vimentin, agrin (glomerular basement protein), and MICA. [76][77][78][79] Jackson et al 80 conducted a study to assess the clinical relevance of donor-specific AECAs using donorderived endothelial precursors.…”

Section: Non-hla Antibodiesmentioning

confidence: 99%

Clinical relevance of antibody development in renal transplantation

Mehra

Siddiqui

Baranwal

et al. 2013

Annals of the New York Academy of Sciences

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The detection and characterization of anti-HLA antibodies and the clinical impact of their appearance following renal transplantation are areas of immense interest. In particular, de novo development of donor-specific antibodies (DSA) has been associated with acute and chronic antibody-mediated graft rejection (AMR). Recently, methods for antibody detection have evolved remarkably from conventional cell-based assays to advanced solid phase systems. These systems have revolutionized the art of defining clinically relevant antibodies that are directed toward a renal graft. While anti-HLA DSAs have been widely associated with poor graft survival, the role of non-HLA antibodies, particularly those directed against endothelial cells, is beginning to be realized. Appreciation of the mechanisms underlying T cell recognition of alloantigens has generated great interest in the use of synthetic peptides to prevent graft rejection. Hopefully, continued progress in unraveling the molecular mechanisms of graft rejection and posttransplant monitoring of antibodies using highly sensitive testing systems will prove beneficial to immunological risk assessment and early prediction of renal allograft failure.

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“…Non‐HLA antibodies against human endothelial progenitor cells (EPC) of the kidney donor can be detected in the blood of renal transplant recipients pre‐ and post‐transplant . Pre‐formed IgG antibodies against donor EPC or isolated targets on EPC were reported to increase the risk of hyperacute rejection, delayed graft function, early acute rejection, chronic graft injury, and graft loss . Graft rejection can occur in the immediate post‐transplant period despite a negative pre‐transplant lymphocyte cross‐match even with HLA‐identical grafts, suggesting that non‐HLA systems, such as major histocompatibility complex class I‐related chain A (MICA), angiotensin II type 1 receptor (anti‐AT1R), endothelin‐1 type A receptor (anti‐ETAR), apoptotic cells, agrin, vimentin, perlecan, Kα‐tubulin, protein kinase Cζ, phospholipid‐binding proteins, and possibly other determinants on endothelial cells, may be targets for acute antibody‐mediated rejection (AMR) or chronic rejection (CR) .…”

Section: Introductionmentioning

confidence: 99%