Isolated De Novo Antiendothelial Cell Antibodies and Kidney Transplant Rejection

Sánchez-Zapardiel, Elena; Mancebo, Esther; Díaz-Ordoñez, María; Huerta, Lucía De Jorge; Ruiz-Martínez, Lara; Serrano, Antonio; Castro-Panete, María José; Utrero‐Rico, Alberto; Andrés, Amado; Morales, José; Domínguez‐Rodríguez, Sara; Paz-Artal, Estela

doi:10.1053/j.ajkd.2016.07.019

Cited by 8 publications

(4 citation statements)

References 32 publications

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“…In general, AECA have been associated with acute and chronic rejection and with early graft dysfunction in different types of solid organ transplant, including heart and kidney. De novo AECA seem to be more strongly associated with ABMR than preformed ones [ 133 ].…”

Section: Armentioning

confidence: 99%

Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction

Quaglia

Merlotti

Guglielmetti

et al. 2020

IJMS

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New biomarkers of early and late graft dysfunction are needed in renal transplant to improve management of complications and prolong graft survival. A wide range of potential diagnostic and prognostic biomarkers, measured in different biological fluids (serum, plasma, urine) and in renal tissues, have been proposed for post-transplant delayed graft function (DGF), acute rejection (AR), and chronic allograft dysfunction (CAD). This review investigates old and new potential biomarkers for each of these clinical domains, seeking to underline their limits and strengths. OMICs technology has allowed identifying many candidate biomarkers, providing diagnostic and prognostic information at very early stages of pathological processes, such as AR. Donor-derived cell-free DNA (ddcfDNA) and extracellular vesicles (EVs) are further promising tools. Although most of these biomarkers still need to be validated in multiple independent cohorts and standardized, they are paving the way for substantial advances, such as the possibility of accurately predicting risk of DGF before graft is implanted, of making a “molecular” diagnosis of subclinical rejection even before histological lesions develop, or of dissecting etiology of CAD. Identification of “immunoquiescent” or even tolerant patients to guide minimization of immunosuppressive therapy is another area of active research. The parallel progress in imaging techniques, bioinformatics, and artificial intelligence (AI) is helping to fully exploit the wealth of information provided by biomarkers, leading to improved disease nosology of old entities such as transplant glomerulopathy. Prospective studies are needed to assess whether introduction of these new sets of biomarkers into clinical practice could actually reduce the need for renal biopsy, integrate traditional tools, and ultimately improve graft survival compared to current management.

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Section: Armentioning

confidence: 99%

Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction

Quaglia

Merlotti

Guglielmetti

et al. 2020

IJMS

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“…Using cultured human umbilical vein as assay to capture the panoply of endothelial reactive antibody, Sun and colleagues reported that 12.6% of a cohort of 174 kidney transplant recipients developed de novo antiendthelial cell antibody (AECA) after transplantation and that this was associated with an increased incidence of acute rejection, and poorer kidney graft function at three years, although differences in actual graft survival were modest (60). A similar relationship between AECA and rejection episodes following kidney transplantation was described recently by Sanchez-Zapardiel (61). Using a proteomics approach, Jackson and colleagues (62) identified four autoantigens (endoglin, Fms-like tyrosine kinase-3 ligand, EGF-like repeats and discoidin I-like domains 3, and intercellular adhesion molecule 4) as potential targets of humoral immunity following kidney transplantation, and reported an increased incidence of AMR in patients with Deleted: three circulating AECA, although, as with the Mohanakumar studies above, patients were also highly sensitised against donor HLA antigen; longer term graft function or outcome was not influenced by AECA status.…”

Section: Characterisation Of Autoantigens Targeted After Transplantationmentioning

confidence: 63%

Humoral autoimmunity after solid organ transplantation: Germinal ideas may not be natural

Siu

Motallebzadeh

Pettigrew

2020

Cellular Immunology

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Non-HLA antibody responses following solid organ transplantation have become increasingly emphasised, with several large clinical series suggesting that such responses contribute to late graft failure. Many of the responses described recognise both recipient and donor moieties of the target antigen and thus represent auto-, rather than allo-immunity. Within this rapidly evolving field, many questions remain unanswered: what triggers the response; how innate and adaptive humoral autoimmunity integrate; and most pressingly, how autoimmunity contributes to graft damage and its relationship to other effector mechanisms of graft rejection. This review summarises recent clinical and experimental studies of humoral autoimmunity in transplant rejection, and considers some of the answers to these questions. Moved (inser,on) [2]Deleted: parental by 3 rd party Deleted: third Deleted: party Field Code Changed Field Code ChangedDeleted: A link with solid organ transplantation and the development of autoimmune-like manifestations was first recognised in the Moved up [2]:A link between autoimmunity and transplantation was first suggested as part of the early murine work characterising the nature of transplant tolerance. It was noted that parental strain mice that were injected intraperitoneally with parental by 3 rd party F1 splenocytes subsequently accepted skin grafts from the third party strain (1), but that growth was retarded in the recipient mice, in association with splenomegaly and evidence of ongoing immunological responsiveness between the F1 donor and parental recipient (2, 3). Lambert et al subsequently reported the development of anti-DNA autoantibody and a systemic lupus erythematosus (SLE)-like disease in such neonatal tolerant mice, with humoral autoimmunity seemingly dependent upon interactions between parental strain CD4 T lymphocytes and F1 strain B cells (4-6)2.1 Historical Perspective

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“…For years, endothelial cell crossmatch has been an approach to detect non-HLA Abs in transplant recipients or waiting list patients [37][38][39][40]. Indeed, many non-HLA Abs are primarily directed to antigens expressed on endothelial cells and have been named anti-Endothelial Cell Abs (AECA).…”

Section: Anti-angiotensin II Type 1 Receptor (At1r) Abs and Anti-endothelin Receptor (Etar) Absmentioning

confidence: 99%

Non-HLA Abs in Solid Organ Transplantation

et al. 2020

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The role of anti-HLA antibodies in solid organ rejection is well established and these antibodies are routinely monitored both in patients in the waiting list and in the post-transplant setting. More recently, the presence of other antibodies directed towards non-HLA antigens, or the so-called minor histocompatibility antigens, has drawn the attention of the transplant community; however, their possible involvement in the graft outcome remains uncertain. These antibodies have been described to possibly have a role in rejection and allograft failure. This review focuses on the most studied non-HLA antibodies and their association with different clinical outcomes considered in solid organ transplantation with the aim of clarifying their clinical implication and potential relevance for routine testing.

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Isolated De Novo Antiendothelial Cell Antibodies and Kidney Transplant Rejection

Cited by 8 publications

References 32 publications

Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction

Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction

Humoral autoimmunity after solid organ transplantation: Germinal ideas may not be natural

Non-HLA Abs in Solid Organ Transplantation

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