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Article ; Online: Second field high-resolution HLA typing for immunologic risk stratification in kidney transplantation.

Senev, Aleksandar / Emonds, Marie-Paule / Naesens, Maarten

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

2021 Volume 21, Issue 10, Page(s) 3502–3503

MeSH term(s)	HLA Antigens/genetics ; Histocompatibility Testing ; Kidney Transplantation ; Risk Assessment
Chemical Substances	HLA Antigens
Language	English
Publishing date	2021-04-30
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2060594-8
ISSN	1600-6143 ; 1600-6135
ISSN (online)	1600-6143
ISSN	1600-6135
DOI	10.1111/ajt.16606
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Article ; Online: Are we underestimating reverse TRALI?

De Clippel, Dorien / Emonds, Marie-Paule / Compernolle, Veerle

Transfusion

2019 Volume 59, Issue 9, Page(s) 2788–2793

Abstract: Background: Transfusion-related acute lung injury (TRALI) is a rare but serious adverse transfusion reaction and is known to be related to anti-human leukocyte antigen (HLA) or anti-human neutrophil antigen (HNA) antibodies in donor plasma. In 2016, ... ...

Abstract	Background: Transfusion-related acute lung injury (TRALI) is a rare but serious adverse transfusion reaction and is known to be related to anti-human leukocyte antigen (HLA) or anti-human neutrophil antigen (HNA) antibodies in donor plasma. In 2016, four of eight reported TRALI cases could not be explained by donor antibodies. It is assumed that fewer than 10% of TRALI cases are triggered by anti-HLA or anti-HNA antibodies in the patient's plasma (reverse TRALI). Study design and methods: Three cases of red blood cell (RBC)-associated and one case of granulocyte-associated TRALI were investigated. Data were collected on the clinical aspects of the patient and the concerned blood product. Patient's HLA antibodies were determined and the implicated donor was contacted for HLA typing. The HLA antibody identification and strength were assessed using a bead assay (Luminex Single Antigen bead assay, Immucor). For HLA typing, a polymerase chain reaction-sequence-specific oligonucleotide method was used that also included Luminex detection. Results: In three RBC-associated TRALI cases, HLA Class I and II antibodies found in the patient's plasma were specific for the HLA type of the transfused leukoreduced blood product. In a fourth case, HLA antibodies were found in a patient who developed TRALI after repeated granulocyte infusions. The HLA antibodies were directed against HLA antigens present on the donor WBCs. Conclusion: The diagnosis of reverse TRALI was retained in four cases, suggesting that reverse TRALI is more frequent than described in the literature, especially in patients with an increased risk for having HLA antibodies.
MeSH term(s)	Acute Lung Injury/epidemiology ; Acute Lung Injury/etiology ; Acute Lung Injury/immunology ; Adult ; Aged ; Diagnostic Errors/statistics & numerical data ; Female ; HLA Antigens/immunology ; Humans ; Isoantibodies/blood ; Male ; Middle Aged ; Prevalence ; Tissue Donors ; Transfusion Reaction/complications ; Transfusion Reaction/epidemiology ; Transfusion Reaction/immunology ; Transfusion-Related Acute Lung Injury/diagnosis ; Transfusion-Related Acute Lung Injury/epidemiology ; Transfusion-Related Acute Lung Injury/etiology
Chemical Substances	HLA Antigens ; Isoantibodies
Language	English
Publishing date	2019-06-26
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	208417-x
ISSN	1537-2995 ; 0041-1132
ISSN (online)	1537-2995
ISSN	0041-1132
DOI	10.1111/trf.15431
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Article ; Online: The Pre-Transplant Non-HLA Antibody Burden Associates With the Development of Histology of Antibody-Mediated Rejection After Kidney Transplantation.

Senev, Aleksandar / Ray, Bryan / Lerut, Evelyne / Hariharan, Jayasree / Heylen, Christine / Kuypers, Dirk / Sprangers, Ben / Emonds, Marie-Paule / Naesens, Maarten

Frontiers in immunology

2022 Volume 13, Page(s) 809059

Abstract: Background: Many kidney allografts fail due to the occurrence of antibody-mediated rejection (ABMR), related to donor-specific anti-HLA antibodies (HLA-DSA). However, the histology of ABMR can also be observed in patients without HLA-DSA. While some non- ...

Abstract	Background: Many kidney allografts fail due to the occurrence of antibody-mediated rejection (ABMR), related to donor-specific anti-HLA antibodies (HLA-DSA). However, the histology of ABMR can also be observed in patients without HLA-DSA. While some non-HLA antibodies have been related to the histology of ABMR, it is not well known to what extent they contribute to kidney allograft injury. Here we aimed to investigate the role of 82 different non-HLA antibodies in the occurrence of histology of ABMR after kidney transplantation. Methods: We included all patients who underwent kidney transplantation between 2004-2013 in a single center and had biobanked serum. Pre- and post-transplant sera (n=2870) were retrospectively tested for the presence of 82 different non-HLA antibodies using a prototype bead assay on Luminex ( Results: 874 patients had available pretransplant sera and were included in this analysis. Of them, 133 (15.2%) received a repeat kidney allograft, and 100 (11.4%) had pretransplant HLA-DSA. In total, 204 (23.3%) patients developed histology of ABMR after kidney transplantation. In 79 patients (38.7%) the histology of ABMR was explained by pretransplant or Conclusions: This study shows that patients highly and broadly sensitized against non-HLA targets are associated with an increased risk of ABMR histology after kidney transplantations in the absence of HLA-DSA. Also, some pretransplant non-HLA autoantibodies are individually associated with increased rates of ABMR histology. However, whether these associations are clinically relevant and represent causality, warrants further studies.
MeSH term(s)	Graft Rejection ; HLA Antigens ; Humans ; Isoantibodies ; Kidney Transplantation/adverse effects ; Retrospective Studies
Chemical Substances	HLA Antigens ; Isoantibodies
Language	English
Publishing date	2022-02-16
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.2022.809059
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Article ; Online: The Clinical Utility of Post-Transplant Monitoring of Donor-Specific Antibodies in Stable Renal Transplant Recipients: A Consensus Report With Guideline Statements for Clinical Practice.

van den Broek, Dennis A J / Meziyerh, Soufian / Budde, Klemens / Lefaucheur, Carmen / Cozzi, Emanuele / Bertrand, Dominique / López Del Moral, Covadonga / Dorling, Anthony / Emonds, Marie-Paule / Naesens, Maarten / de Vries, Aiko P J

Transplant international : official journal of the European Society for Organ Transplantation

2023 Volume 36, Page(s) 11321

Abstract: Solid phase immunoassays improved the detection and determination of the antigen-specificity of donor-specific antibodies (DSA) to human leukocyte antigens (HLA). The widespread use of SPI in kidney transplantation also introduced new clinical dilemmas, ... ...

Abstract	Solid phase immunoassays improved the detection and determination of the antigen-specificity of donor-specific antibodies (DSA) to human leukocyte antigens (HLA). The widespread use of SPI in kidney transplantation also introduced new clinical dilemmas, such as whether patients should be monitored for DSA pre- or post-transplantation. Pretransplant screening through SPI has become standard practice and DSA are readily determined in case of suspected rejection. However, DSA monitoring in recipients with stable graft function has not been universally established as standard of care. This may be related to uncertainty regarding the clinical utility of DSA monitoring as a screening tool. This consensus report aims to appraise the clinical utility of DSA monitoring in recipients without overt signs of graft dysfunction, using the Wilson & Junger criteria for assessing the validity of a screening practice. To assess the evidence on DSA monitoring, the European Society for Organ Transplantation (ESOT) convened a dedicated workgroup, comprised of experts in transplantation nephrology and immunology, to review relevant literature. Guidelines and statements were developed during a consensus conference by Delphi methodology that took place in person in November 2022 in Prague. The findings and recommendations of the workgroup on subclinical DSA monitoring are presented in this article.
MeSH term(s)	Humans ; Kidney Transplantation ; Graft Rejection ; Isoantibodies ; Kidney ; Organ Transplantation ; HLA Antigens ; Graft Survival ; Transplant Recipients ; Tissue Donors ; Histocompatibility Testing ; Retrospective Studies
Chemical Substances	Isoantibodies ; HLA Antigens
Language	English
Publishing date	2023-07-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	639435-8
ISSN	1432-2277 ; 0934-0874
ISSN (online)	1432-2277
ISSN	0934-0874
DOI	10.3389/ti.2023.11321
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Article ; Online: The evolution of histological changes suggestive of antibody-mediated injury, in the presence and absence of donor-specific anti-HLA antibodies.

Coemans, Maarten / Senev, Aleksandar / Van Loon, Elisabet / Lerut, Evelyne / Sprangers, Ben / Kuypers, Dirk / Emonds, Marie-Paule / Verbeke, Geert / Naesens, Maarten

Transplant international : official journal of the European Society for Organ Transplantation

2021 Volume 34, Issue 10, Page(s) 1824–1836

Abstract: The interplay between donor-specific anti-HLA antibodies (HLA-DSA), histology of active antibody-mediated rejection ( ... ...

Abstract	The interplay between donor-specific anti-HLA antibodies (HLA-DSA), histology of active antibody-mediated rejection (aABMR
MeSH term(s)	Cohort Studies ; Graft Rejection ; Graft Survival ; HLA Antigens ; Humans ; Isoantibodies ; Kidney Transplantation ; Tissue Donors
Chemical Substances	HLA Antigens ; Isoantibodies
Language	English
Publishing date	2021-09-12
Publishing country	England
Document type	Journal Article
ZDB-ID	639435-8
ISSN	1432-2277 ; 0934-0874
ISSN (online)	1432-2277
ISSN	0934-0874
DOI	10.1111/tri.13964
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Article ; Online: Unravelling the immune signature of herpes zoster: Insights into pathophysiology and the HLA risk profile.

Vandoren, Romi / Boeren, Marlies / Schippers, Jolien / Bartholomeus, Esther / Mullan, Kerry / Michels, Nele / Aerts, Olivier / Leysen, Julie / Bervoets, An / Lambert, Julien / Leuridan, Elke / Wens, Johan / Peeters, Karin / Emonds, Marie-Paule / Jansens, Hilde / Casanova, Jean-Laurent / Bastard, Paul / Suls, Arvid / Van Tendeloo, Viggo /

Ponsaerts, Peter / Delputte, Peter / Ogunjimi, Benson / Laukens, Kris / Meysman, Pieter

The Journal of infectious diseases

2024

Abstract: The varicella-zoster virus (VZV) infects over 95% of the population. VZV reactivation causes herpes zoster (HZ), known as shingles, primarily affecting the elderly and immunocompromised individuals. However, HZ can also occur in otherwise healthy ... ...

Abstract	The varicella-zoster virus (VZV) infects over 95% of the population. VZV reactivation causes herpes zoster (HZ), known as shingles, primarily affecting the elderly and immunocompromised individuals. However, HZ can also occur in otherwise healthy individuals. We analyzed the immune signature and risk profile in HZ patients using a genome-wide association study across different UK Biobank HZ cohorts. Additionally, we conducted one of the largest HZ HLA association studies to date, coupled with transcriptomic analysis of pathways underlying HZ susceptibility. Our findings highlight the significance of the MHC locus for HZ development, identifying five protective and four risk HLA alleles. This demonstrates that HZ susceptibility is largely governed by variations in the MHC. Furthermore, functional analyses revealed the upregulation of type I interferon and adaptive immune responses. These findings provide fresh molecular insights into the pathophysiology and the activation of innate and adaptive immune responses triggered by symptomatic VZV reactivation.
Language	English
Publishing date	2024-01-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiad609
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Article ; Online: Histological picture of ABMR without HLA-DSA: Temporal dynamics of effector mechanisms are relevant in disease reclassification.

Senev, Aleksandar / Callemeyn, Jasper / Lerut, Evelyne / Emonds, Marie-Paule / Naesens, Maarten

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

2019 Volume 19, Issue 3, Page(s) 954–955

MeSH term(s)	Antibodies ; Antilymphocyte Serum ; Humans ; Tissue Donors
Chemical Substances	Antibodies ; Antilymphocyte Serum
Language	English
Publishing date	2019-01-24
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	2060594-8
ISSN	1600-6143 ; 1600-6135
ISSN (online)	1600-6143
ISSN	1600-6135
DOI	10.1111/ajt.15234
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Article ; Online: Allogeneic Hematopoietic Stem Cell Transplantation After Prior Lung Transplantation for Hereditary Pulmonary Alveolar Proteinosis: A Case Report.

Beeckmans, Hanne / Ambrocio, Gene P L / Bos, Saskia / Vermaut, Astrid / Geudens, Vincent / Vanstapel, Arno / Vanaudenaerde, Bart M / De Baets, Frans / Malfait, Thomas L A / Emonds, Marie-Paule / Van Raemdonck, Dirk E / Schoemans, Hélène M / Vos, Robin

Frontiers in immunology

2022 Volume 13, Page(s) 931153

Abstract: Pulmonary alveolar proteinosis (PAP) is a rare, diffuse lung disorder characterized by surfactant accumulation in the small airways due to defective clearance by alveolar macrophages, resulting in impaired gas exchange. Whole lung lavage is the current ... ...

Abstract	Pulmonary alveolar proteinosis (PAP) is a rare, diffuse lung disorder characterized by surfactant accumulation in the small airways due to defective clearance by alveolar macrophages, resulting in impaired gas exchange. Whole lung lavage is the current standard of care treatment for PAP. Lung transplantation is an accepted treatment option when whole lung lavage or other experimental treatment options are ineffective, or in case of extensive pulmonary fibrosis secondary to PAP. A disadvantage of lung transplantation is recurrence of PAP in the transplanted lungs, especially in hereditary PAP. The hereditary form of PAP is an ultra-rare condition caused by genetic mutations in genes encoding for the granulocyte macrophage-colony stimulating factor (GM-CSF) receptor, and intrinsically affects bone marrow derived-monocytes, which differentiate into macrophages in the lung. Consequently, these macrophages typically display disrupted GM-CSF receptor-signaling, causing defective surfactant clearance. Bone marrow/hematopoietic stem cell transplantation may potentially reverse the lung disease in hereditary PAP. In patients with hereditary PAP undergoing lung transplantation, post-lung transplant recurrence of PAP may theoretically be averted by subsequent hematopoietic stem cell transplantation, which results in a graft-versus-
MeSH term(s)	Hematopoietic Stem Cell Transplantation ; Humans ; Lung Transplantation ; Pulmonary Alveolar Proteinosis/drug therapy ; Pulmonary Alveolar Proteinosis/therapy ; Pulmonary Fibrosis ; Pulmonary Surfactants/therapeutic use ; Quality of Life ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/genetics ; Surface-Active Agents/therapeutic use
Chemical Substances	Pulmonary Surfactants ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor ; Surface-Active Agents
Language	English
Publishing date	2022-07-14
Publishing country	Switzerland
Document type	Case Reports ; 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.2022.931153
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Article ; Online: Bortezomib for autoimmune hemolytic anemia after intestinal transplantation.

Knops, Noël / Emonds, Marie-Paule / Herman, Jean / Levtchenko, Elena / Mekahli, Djalila / Pirenne, Jacques / Van Geet, Chris / Dierickx, Daan

Pediatric transplantation

2020 Volume 24, Issue 4, Page(s) e13700

Abstract: AIHA is rare in the general population and associated with a mortality of 8%. In contrast, AIHA occurs in up to 12.2% of cases after intestinal transplantation and is associated with mortality up to 50%. Treatment entails a "step-up" approach including ... ...

Abstract	AIHA is rare in the general population and associated with a mortality of 8%. In contrast, AIHA occurs in up to 12.2% of cases after intestinal transplantation and is associated with mortality up to 50%. Treatment entails a "step-up" approach including corticosteroids, IvIg, plasmapheresis, and rituximab. However, AIHA after transplantation often is refractory to this strategy, contributing to a poor outcome. We describe a child with microvillous inclusion disease who developed AIHA 1 year after multivisceral transplantation that was refractory to standard therapy and was subsequently treated with bortezomib.We observed remission of AIHA within 1 week after the start of bortezomib. Bortezomib was associated with transient diarrhea, leucopenia, and elevated liver enzymes. Three years later, he remains in remission without important complications. Published data on bortezomib for autoimmune cytopenias outside SOT are discussed. This is the first report to support bortezomib as an important therapeutic alternative for AIHA after SOT. The occurrence and treatment of AIHA after SOT, and specifically intestinal transplantation, should be the subject of future registry studies to collect additional experience and explore the optimal therapeutic approach.
MeSH term(s)	Anemia, Hemolytic, Autoimmune/drug therapy ; Bortezomib/therapeutic use ; Child, Preschool ; Humans ; Intestines/transplantation ; Male ; Postoperative Complications/drug therapy
Chemical Substances	Bortezomib (69G8BD63PP)
Language	English
Publishing date	2020-03-12
Publishing country	Denmark
Document type	Case Reports ; Journal Article
ZDB-ID	1390284-2
ISSN	1399-3046 ; 1397-3142
ISSN (online)	1399-3046
ISSN	1397-3142
DOI	10.1111/petr.13700
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Zs.A 4947: Show issues

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Article ; Online: Clinical importance of extended second field high-resolution HLA genotyping for kidney transplantation.

Senev, Aleksandar / Emonds, Marie-Paule / Van Sandt, Vicky / Lerut, Evelyne / Coemans, Maarten / Sprangers, Ben / Kuypers, Dirk / Naesens, Maarten

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

2020 Volume 20, Issue 12, Page(s) 3367–3378

Abstract: The need for extended second field high-resolution (2F-HR) HLA genotyping in kidney transplantation is debated. In a cohort of 1000 kidney transplants, we evaluated the impact of different HLA genotyping levels on the assignment of donor-specific anti- ... ...

Abstract	The need for extended second field high-resolution (2F-HR) HLA genotyping in kidney transplantation is debated. In a cohort of 1000 kidney transplants, we evaluated the impact of different HLA genotyping levels on the assignment of donor-specific anti-HLA antibodies (DSA) and investigated whether inference of 2F-HR genotypes from low-resolution (LR) genotypes could be used to correctly assign DSA. Based on LR genotypes, 224 pretransplant DSAs were present in 140 patients and absent in 860 patients (DSA
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Genotype ; Graft Rejection/etiology ; Graft Rejection/genetics ; Graft Survival ; HLA Antigens/genetics ; Histocompatibility Testing ; Humans ; Isoantibodies ; Kidney Transplantation/adverse effects ; Male ; Middle Aged ; Risk Factors ; Tissue Donors ; Young Adult
Chemical Substances	HLA Antigens ; Isoantibodies
Language	English
Publishing date	2020-05-15
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.15938
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