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Article ; Online: The highlights of kidney transplantation in 2023

De Serres, Sacha A / Couzi, Lionel

2024 Volume 20, Issue S1, Page(s) 1–9

Abstract: In 2023, significant advances were made in various areas of kidney transplantation. Firstly, the use of a balanced crystalloid solution in the recipient appears to prevent the delay in graft function, unlike hypothermia in the donor and normothermic ... ...

Title translation	Les temps forts de la transplantation rénale en 2023
Abstract	In 2023, significant advances were made in various areas of kidney transplantation. Firstly, the use of a balanced crystalloid solution in the recipient appears to prevent the delay in graft function, unlike hypothermia in the donor and normothermic pulsatile perfusion. Understanding the pathophysiology of humoral rejection has progressed, highlighting the major role of HLA class II molecules and innate immune cells (NK and monocytes expressing FCGR3A). An automatic Banff classification algorithm has been developed to better categorize biopsies in currently known diagnoses. CXCL10, combined with other variables, seems effective in ruling out rejection, but its role in routine care is yet to be defined. Regarding cytomegalovirus (CMV), letermovir has been proven effective in preventing CMV disease in D+R- patients, with fewer hematological side effects. For R+ patients, monitoring CMV-specific T-cell immunity is suggested to reduce the duration of antiviral prophylaxis. The only innovation in immunosuppression is imlifidase for highly sensitized patients, guided by French recommendations. A new equation for glomerular filtration rate measurement has been developed for kidney transplant recipients, performing well across various analyzed stratifications. Finally, xenotransplantation is making a comeback this year, generating hope. However, the description of early humoral rejections involving innate immune cells indicates that adjustments are still needed before considering its widespread deployment.
MeSH term(s)	Humans ; Kidney Transplantation/adverse effects ; Antiviral Agents/therapeutic use ; Cytomegalovirus Infections/drug therapy ; Cytomegalovirus ; Immunosuppressive Agents/therapeutic use ; Graft Rejection/prevention & control
Chemical Substances	Antiviral Agents ; Immunosuppressive Agents
Language	French
Publishing date	2024-01-31
Publishing country	France
Document type	Journal Article
ZDB-ID	2229575-6
ISSN	1872-9177 ; 1769-7255
ISSN (online)	1872-9177
ISSN	1769-7255
DOI	10.1684/ndt.2024.63
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Zs.A 6298: Show issues

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Article ; Online: SARS-Cov-2 Antibody Levels That Confer Immune Protection Based on Neutralization of the Omicron Variant.

Desgagnés, Jean-Simon / Désy, Olivier / Thivierge, Marie-Pier / Marcoux, Meagan / Béland, Stéphanie / De Serres, Sacha A

Transplantation

2023 Volume 107, Issue 6, Page(s) e184–e185

MeSH term(s)	Humans ; SARS-CoV-2 ; COVID-19 ; Antibodies, Viral ; Antibodies, Neutralizing
Chemical Substances	Antibodies, Viral ; Antibodies, Neutralizing
Language	English
Publishing date	2023-05-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	208424-7
ISSN	1534-6080 ; 0041-1337
ISSN (online)	1534-6080
ISSN	0041-1337
DOI	10.1097/TP.0000000000004596
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Zs.A 488: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: T follicular helper cells expansion in transplant recipients correlates with graft infiltration and adverse outcomes.

Désy, Olivier / Béland, Stéphanie / Thivierge, Marie-Pier / Marcoux, Meagan / Desgagnés, Jean-Simon / Bouchard-Boivin, François / Gama, Alcino / Riopel, Julie / Latulippe, Eva / De Serres, Sacha A

Frontiers in immunology

2024 Volume 15, Page(s) 1275933

Abstract: Introduction: The process of immunization following vaccination in humans bears similarities to that of immunization with allografts. Whereas vaccination aims to elicit a rapid response, in the transplant recipient, immunosuppressants slow the ... ...

Abstract	Introduction: The process of immunization following vaccination in humans bears similarities to that of immunization with allografts. Whereas vaccination aims to elicit a rapid response, in the transplant recipient, immunosuppressants slow the immunization to alloantigens. The induction of CD4+CXCR5+ T follicular helper (Tfh) cells has been shown to correlate with the success of vaccine immunization. Method: We studied a cohort of 65 transplant recipients who underwent histological evaluation concurrent with PBMC isolation and follow-up sampling to investigate the phenotypic profiles in the blood and allotissue and analyze their association with clinical events. Results: The proportion of circulating Tfh cells was heterogeneous over time. Patients in whom this compartment increased had lower CCR7-PD1+CD4+CXCR5+ T cells during follow-up. These patients exhibited more alloreactive CD4+ T cells using HLA-DR-specific tetramers and a greater proportion of detectable circulating plasmablasts than the controls. Examination of baseline biopsies revealed that expansion of the circulating Tfh compartment did not follow prior intragraft leukocyte infiltration. However, multicolor immunofluorescence microscopy of the grafts showed a greater proportion of CXCR5+ T cells than in the controls. CD4+CXCR5+ cells were predominantly PD1+ and were in close contact with B cells in situ. Despite clinical stability at baseline, circulating Tfh expansion was associated with a higher risk of a composite of anti-HLA donor-specific antibodies, rejection, lower graft function, or graft loss. Conclusion: In otherwise stable patients post-transplant, circulating Tfh expansion can identify ongoing alloreactivity, detectable before allograft injury. Tfh expansion is relevant clinically because it predicts poor graft prognosis. These findings have implications for immune surveillance.
MeSH term(s)	Humans ; T-Lymphocytes, Helper-Inducer ; T Follicular Helper Cells ; Transplant Recipients ; Leukocytes, Mononuclear ; CD4-Positive T-Lymphocytes ; Antilymphocyte Serum
Chemical Substances	Antilymphocyte Serum
Language	English
Publishing date	2024-02-07
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2024.1275933
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Article ; Online: Endothelial colony forming cells generated from cryopreserved peripheral blood mononuclear cells.

Béland, Stéphanie / Désy, Olivier / Bouchard-Boivin, François / Gama, Alcino / De Serres, Sacha A

Human immunology

2021 Volume 82, Issue 4, Page(s) 309–314

Abstract: Derivation of endothelial colony forming cells (ECFCs) from peripheral blood mononuclear cells (PBMCs) is a technique that could provide access to donor endothelial cells to study donor endothelium/recipient immune cells interactions. The success rate of ...

Abstract	Derivation of endothelial colony forming cells (ECFCs) from peripheral blood mononuclear cells (PBMCs) is a technique that could provide access to donor endothelial cells to study donor endothelium/recipient immune cells interactions. The success rate of ECFC colony formation from cryopreserved PBMCs has not been reported. We used biobanked PBMCs and studied the yield of ECFC generation. Endothelial phenotype was confirmed with CD31, CD146, CD309, CD34, CD14 and CD11c staining by flow cytometry and VE-cadherin, von Willebrand factor and Dil-Ac-LDL by fluorescent microscopy. Functionality was tested by endothelial cell tube-based formation assay. The success rate of ECFC generation was 28%. Freezing time was not a predictor of ECFC generation while a shorter time on dialysis and living transplant were significant determinants. These data suggest that it is possible to generate ECFCs from cryopreserved PBMCs, which is a potentially useful option for the longitudinal assessment of alloimmune response in transplantation.
MeSH term(s)	Cells, Cultured ; Colony-Forming Units Assay ; Cryopreservation/methods ; Endothelial Cells/metabolism ; Endothelial Cells/pathology ; Endothelial Progenitor Cells/metabolism ; Endothelial Progenitor Cells/pathology ; Graft Rejection/immunology ; Humans ; Immunity ; Kidney Transplantation ; Leukocytes, Mononuclear/immunology ; Phenotype ; Transplantation, Homologous
Language	English
Publishing date	2021-02-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	801524-7
ISSN	1879-1166 ; 0198-8859
ISSN (online)	1879-1166
ISSN	0198-8859
DOI	10.1016/j.humimm.2021.02.009
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Zs.A 1597: Show issues

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Article: The Progression of Interstitial Fibrosis and Tubular Atrophy at 6 Months Is an Independent Predictor of Poor Graft Outcomes in Kidney Transplant Recipients.

Ouellet, Gabriel / Houde, Isabelle / Riopel, Julie / Latulippe, Eva / Douville, Pierre / Lesage, Julie / Côté, Isabelle / Lapointe, Isabelle / De Serres, Sacha A

Transplantation direct

2022 Volume 8, Issue 12, Page(s) e1375

Abstract: Interstitial fibrosis and tubular atrophy (IFTA) found on 1-y surveillance biopsies has been associated with poor graft outcomes. However, its progression over time and relationship to outcomes are less well defined.: Methods: We studied implantation ... ...

Abstract	Interstitial fibrosis and tubular atrophy (IFTA) found on 1-y surveillance biopsies has been associated with poor graft outcomes. However, its progression over time and relationship to outcomes are less well defined. Methods: We studied implantation and 6-mo surveillance biopsies and examined the association between the progression of IFTA (ΔIFTA) and a composite of censored graft loss or doubling of serum creatinine in 248 adult kidney recipients. Results: The percentage of patients with ΔIFTA of 1 or ≥2 was 35% and 22%, respectively. Positive ΔIFTA was a risk factor for the composite endpoint (hazard ratio, 1.36; 95% confidence interval, 1.03-1.79). This estimate was robust to adjustment for recipient and donor baseline characteristics, baseline IFTA, tacrolimus levels, and rejection status. ΔIFTA was associated with decreased estimated glomerular filtration rate at 3 and 5 y. IFTA+i was a predictor in the cohort; however, IFTA progression was not limited to those with a mononuclear cell interstitial inflammation (Banff "i") score above zero. Notably, donor age was a predictor of IFTA at 6 mo, but not of ΔIFTA, whereas rejection, donor diabetes, and recipient smoking status were. Conclusions: Progression of IFTA at 6 mo can predict outcomes. ΔIFTA was not related to donor age but may be linked to other risk factors influencing decision-making for donor versus recipient selection.
Language	English
Publishing date	2022-11-04
Publishing country	United States
Document type	Journal Article
ISSN	2373-8731
ISSN	2373-8731
DOI	10.1097/TXD.0000000000001375
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Article ; Online: [No title information]

Hall, Victoria G / Solera, Javier T / Al-Alahmadi, Ghadeer / Marinelli, Tina / Cardinal, Héloïse / Poirier, Charles / Huard, Geneviève / Prasad, G V Ramesh / De Serres, Sacha A / Isaac, Debra / Mainra, Rahul / Lamarche, Caroline / Sapir-Pichhadze, Ruth / Gilmour, Susan / Humar, Atul / Kumar, Deepali

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne

2022 Volume 194, Issue 46, Page(s) E1578–E1586

Title translation	Gravité de la COVID-19 chez les receveurs d’une transplantation d’organe plein au Canada, 2020–2021 : étude de cohorte prospective multicentrique.
MeSH term(s)	Humans ; COVID-19 ; Prospective Studies ; Transplant Recipients ; Canada ; Organ Transplantation
Language	French
Publishing date	2022-11-28
Publishing country	Canada
Document type	Multicenter Study ; Journal Article
ZDB-ID	215506-0
ISSN	1488-2329 ; 0008-4409 ; 0820-3946
ISSN (online)	1488-2329
ISSN	0008-4409 ; 0820-3946
DOI	10.1503/cmaj.220620-f
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Article: Immunogenicity, Safety, and Breakthrough Severe Acute Respiratory Syndrome Coronavirus 2 Infections After Coronavirus Disease 2019 Vaccination in Organ Transplant Recipients: A Prospective Multicenter Canadian Study.

Kabbani, Dima / Yotis, Demitra M / Ferreira, Victor H / Shalhoub, Sarah / Belga, Sara / Tyagi, Varalika / Ierullo, Matthew / Kulasingam, Vathany / Hébert, Marie-Josée / West, Lori / Delisle, Jean-Sébastien / Racine, Normand / De Serres, Sacha A / Cardinal, Héloïse / Dieudé, Mélanie / Humar, Atul / Kumar, Deepali

Open forum infectious diseases

2023 Volume 10, Issue 5, Page(s) ofad200

Abstract: Background: Solid organ transplant (SOT) recipients are at risk for severe coronavirus disease 2019 (COVID-19), despite vaccination. Our study aimed to elucidate COVID-19 vaccine immunogenicity and evaluate adverse events such as hospitalization, ... ...

Abstract	Background: Solid organ transplant (SOT) recipients are at risk for severe coronavirus disease 2019 (COVID-19), despite vaccination. Our study aimed to elucidate COVID-19 vaccine immunogenicity and evaluate adverse events such as hospitalization, rejection, and breakthrough infection in a SOT cohort. Methods: We performed a prospective, observational study on 539 adult SOT recipients (age ≥18 years old) recruited from 7 Canadian transplant centers. Demographics including transplant characteristics, vaccine types, and immunosuppression and events such as hospitalization, infection, and rejection were recorded. Follow ups occurred every 4-6 weeks postvaccination and at 6 and 12 months from first dose. Serum was processed from whole blood to measure anti-receptor binding domain (RBD) antibodies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein to assess immunogenicity. Results: The COVID-19 vaccines were found to be safe in SOT recipients with low rates of rejection requiring therapy (0.7%). Immunogenicity improved after the third vaccine dose, yet 21% developed no anti-RBD response. Factors such as older age, lung transplantation, chronic kidney disease, and shorter duration from transplant were associated with decreased immunogenicity. Patients with at least 3 doses were protected from hospitalization when experiencing breakthrough infections. Significantly increased anti-RBD levels were observed in patients who received 3 doses and had breakthrough infection. Conclusions: Three or four doses of COVID-19 vaccines were safe, increased immunogenicity, and protected against severe disease requiring hospitalization. Infection paired with multiple vaccinations significantly increased anti-RBD response. However, SOT populations should continue to practice infection prevention measures, and they should be prioritized for SARS-CoV-2 pre-exposure prophylactics and early therapeutics.
Language	English
Publishing date	2023-04-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2757767-3
ISSN	2328-8957
ISSN	2328-8957
DOI	10.1093/ofid/ofad200
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Article ; Online: TNF-α Production by Monocytes Stimulated With Epstein-Barr Virus-Peptides as a Marker of Immunosuppression-Related Adverse Events in Kidney Transplant Recipients.

Bouchard-Boivin, François / Désy, Olivier / Béland, Stéphanie / Houde, Isabelle / De Serres, Sacha A

Kidney international reports

2019 Volume 4, Issue 10, Page(s) 1446–1453

Abstract: Introduction: Infections and cancers now outnumber rejection as a cause of morbidity in transplant recipients, likely as a result of over-immunosuppression. Currently, there is no clinical tool to detect over-immunosuppression. We recently reported that ...

Abstract	Introduction: Infections and cancers now outnumber rejection as a cause of morbidity in transplant recipients, likely as a result of over-immunosuppression. Currently, there is no clinical tool to detect over-immunosuppression. We recently reported that tumor necrosis factor alpha (TNF-α) production by CD14 Methods: We conducted a pilot study the assay using 142 peripheral blood mononuclear samples from a cohort of 71 kidney transplant recipients. Patients were classified as cases or controls according to the occurrence of opportunistic infection, recurring bacterial infections or Results: Cases were detected with 83% sensitivity and 68% specificity. The negative predictive value of the assay was 89%. The hazard ratio for the occurrence of the endpoint was 6.8 (95% confidence interval 2.0-23.9; Conclusion: These data validate this cell-based assay as a promising tool for personalizing immunotherapy. Studies are under way for a 2-step assay with improved specificity.
Language	English
Publishing date	2019-07-19
Publishing country	United States
Document type	Journal Article
ISSN	2468-0249
ISSN (online)	2468-0249
DOI	10.1016/j.ekir.2019.07.007
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Article ; Online: Expression of Class II Human Leukocyte Antigens on Human Endothelial Cells Shows High Interindividual and Intersubclass Heterogeneity.

Béland, Stéphanie / Désy, Olivier / El Fekih, Rania / Marcoux, Meagan / Thivierge, Marie-Pier / Desgagné, Jean-Simon / Latulippe, Eva / Riopel, Julie / Wagner, Eric / Rennke, Helmut G / Weins, Astrid / Yeung, Melissa / Lapointe, Isabelle / Azzi, Jamil / De Serres, Sacha A

Journal of the American Society of Nephrology : JASN

2023 Volume 34, Issue 5, Page(s) 846–856

Abstract: Significance statement: Donor-specific antibodies against class II HLA are a major cause of chronic kidney graft rejection. Nonetheless, some patients presenting with these antibodies remain in stable histological and clinical condition. This study ... ...

Abstract	Significance statement: Donor-specific antibodies against class II HLA are a major cause of chronic kidney graft rejection. Nonetheless, some patients presenting with these antibodies remain in stable histological and clinical condition. This study describes the use of endothelial colony-forming cell lines to test the hypothesis of the heterogeneous expression of HLA molecules on endothelial cells in humans. Flow cytometry and immunofluorescence staining revealed substantial interindividual and interlocus variability, with HLA-DQ the most variable. Our data suggest that the expression of HLA class II is predicted by locus. The measurement of endothelial expression of HLA class II in the graft could present a novel paradigm in the evaluation of the alloimmune risk in transplantation and certain diseases. Background: HLA antigens are important targets of alloantibodies and allospecific T cells involved in graft rejection. Compared with research into understanding alloantibody development, little is known about the variability in expression of their ligands on endothelial cells. We hypothesized individual variability in the expression of HLA molecules. Methods: We generated endothelial colony forming cell lines from human peripheral blood mononuclear cells ( n =39). Flow cytometry and immunofluorescence staining were used to analyze the cells, and we assessed the relationship between HLA-DQ expression and genotype. Two cohorts of kidney transplant recipients were analyzed to correlate HLA-DQ mismatches with the extent of intragraft microvascular injury. Results: Large variability was observed in the expression of HLA class II antigens, not only between individuals but also between subclasses. In particular, HLA-DQ antigens had a low and heterogeneous expression, ranging from 0% to 85% positive cells. On a within-patient basis, this expression was consistent between endothelial cell colonies and antigen-presenting cells. HLA-DQ5 and -DQ6 were associated with higher levels of expression, whereas HLA-DQ7, -DQ8, and -DQ9 with lower. HLA-DQ5 mismatches among kidney transplant recipients were associated with significant increase in graft microvascular. Conclusion: These data challenge the current paradigm that HLA antigens, in particular HLA class II, are a single genetic and post-translational entity. Understanding and assessing the variability in the expression of HLA antigens could have clinical monitoring and treatment applications in transplantation, autoimmune diseases, and oncology.
MeSH term(s)	Humans ; Endothelial Cells ; Leukocytes, Mononuclear ; Kidney Transplantation ; HLA Antigens ; HLA-DQ Antigens ; Isoantibodies ; Graft Rejection ; Histocompatibility Antigens Class II ; Graft Survival
Chemical Substances	HLA Antigens ; HLA-DQ Antigens ; Isoantibodies ; Histocompatibility Antigens Class II
Language	English
Publishing date	2023-02-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1085942-1
ISSN	1533-3450 ; 1046-6673
ISSN (online)	1533-3450
ISSN	1046-6673
DOI	10.1681/ASN.0000000000000095
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Article ; Online: Longitudinal immune profile reveals reduced function of pro-inflammatory monocytes with age following kidney transplantation.

Désy, Olivier / Vallin, Patrice / Béland, Stéphanie / Bouchard-Boivin, François / Gama, Alcino P / De Serres, Sacha A

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

2020 Volume 21, Issue 3, Page(s) 1147–1159

Abstract: ... 300 PBMC samples collected longitudinally in 45 de novo, adult kidney recipients and performed ...

Abstract	Toxicity of immunosuppression, notably the risk of infection, increases with age. However, the dynamic changes in innate immune response following transplantation are unclear. Based on recent observations, we hypothesized that pro-inflammatory capacity would decrease with age. We analyzed approximately 300 PBMC samples collected longitudinally in 45 de novo, adult kidney recipients and performed detailed phenotypic and functional profiling of monocytes and T cell subsets. Inflammatory response to TLR4 stimulation and indirect allostimulation using mismatched HLA peptides were assessed. In patients aged ≥56 years, TNF-α production by intermediate monocytes was similar to that in younger patients early posttransplant, but diminished substantially later. Adjusted analyses suggested that this was not attributable to confounding factors. In contrast, the alloimmune response to HLA peptides measured by IFN-γ in CD4
MeSH term(s)	Adult ; Aged ; Histocompatibility ; Humans ; Immunosuppressive Agents ; Kidney Transplantation/adverse effects ; Leukocytes, Mononuclear ; Monocytes
Chemical Substances	Immunosuppressive Agents
Language	English
Publishing date	2020-09-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2060594-8
ISSN	1600-6143 ; 1600-6135
ISSN (online)	1600-6143
ISSN	1600-6135
DOI	10.1111/ajt.16249
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