Article
Urology & Nephrology
Adrienne Seitz, Katherine Mounsey, Pamela Hughes, Katherine Cullen, Matthew Welberry Smith, Sunil Daga, Clive Carter, Brendan Clark, Richard Baker
Summary: This study aimed to evaluate the clinical outcomes of renal transplants with pre-existing isolated HLA-DP-DSAs. The results showed that the presence of HLA-DP-DSAs was a major factor associated with antibody-mediated rejection, and patients with HLA-DP-DSAs showed more severe pathological changes on biopsy.
KIDNEY INTERNATIONAL REPORTS
(2022)
Article
Surgery
Timothee Laboux, Remi Lenain, Jonathan Visentin, Gauthier Flahaut, Paul Chamley, Francois Provot, Isabelle Top, Clarisse Kerleau, Myriam Labalette, Gabriel Choukroun, Lionel Couzi, Gilles Blancho, Marc Hazzan, Mehdi Maanaoui
Summary: The presence of preformed donor specific antibodies (DSA) is a risk factor for acute antibody-mediated rejection (aABMR) in kidney transplantation. Specifically, HLA-DP DSA is associated with a higher risk of aABMR compared to HLA-Cw DSA. The risk of aABMR is also influenced by the level of DSA's mean fluorescence intensity (MFI) on the day of transplant. These findings suggest the importance of considering these antibodies in organ allocation algorithms.
TRANSPLANT INTERNATIONAL
(2023)
Article
Immunology
Suzanne Bezstarosti, Cynthia S. M. Kramer, Marry E. I. Franke-van Dijk, Manon Vergunst, Kim H. Bakker, Merve Uyar-Mercankaya, Rico Buchli, Dave L. Roelen, Johan W. de Fijter, Frans H. J. Claas, Sebastiaan Heidt
Summary: HLA-DQ donor-specific antibodies (DSA) play a significant role in renal transplantation, and this study focuses on isolating HLA-DQ specific memory B cells to generate monoclonal antibodies that can verify the recognition of eplets on HLA molecules. The findings provide valuable insights into the epitopes of HLA-DQ, contributing to the understanding of HLA-DQ alloantibody pathogenicity in transplantation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell & Tissue Engineering
Tomoyasu Jo, Yasuyuki Arai, Kazuo Hatanaka, Hiroyuki Ishii, Akiko Ono, Nobuki Matsuyama, Jumpei Mori, Yangsook Koh, Fumihiro Azuma, Takafumi Kimura
Summary: This study examined the impact of anti-HLA antibodies against HLA-DP and -DQ on cord-blood transplantation outcomes. The presence of DSAs against HLA-DP and -DQ was associated with lower engraftment rates, longer engraftment time, increased risk of bacterial infection, and reduced survival after transplantation.
Article
Pediatrics
Alexander Fichtner, Caner Suesal, Britta Hoeker, Susanne Rieger, Ruediger Waldherr, Jens H. Westhoff, Anja Sander, Duska Dragun, Burkhard Toenshoff
Summary: In pediatric kidney transplant recipients, a high prevalence of non-HLA antibodies was observed. Antibodies against AT(1)R, ETAR, and MICA were associated with the histological phenotype of ABMR. The cumulative load of HLA-DSA and non-HLA antibodies in circulation was related to the degree of microinflammation in peritubular capillaries, and non-HLA antibody positivity was an independent risk factor for graft function deterioration.
PEDIATRIC NEPHROLOGY
(2021)
Article
Medicine, General & Internal
Covadonga Lopez del Moral, Kaiyin Wu, Marcel Naik, Bilgin Osmanodja, Aylin Akifova, Nils Lachmann, Diana Stauch, Sabine Hergovits, Mira Choi, Friederike Bachmann, Fabian Halleck, Eva Schrezenmeier, Danilo Schmidt, Klemens Budde
Summary: This study provides a comprehensive analysis of the natural course of dnDSA after kidney transplantation, demonstrates the impact of MFI evolution on graft outcomes, and identifies a subgroup of patients with a stable disappearance of dnDSA associated with better allograft survival.
FRONTIERS IN MEDICINE
(2022)
Article
Immunology
Shengli Song, Miriam Manook, Jean Kwun, Annette M. Jackson, Stuart J. Knechtle, Garnett Kelsoe
Summary: Antibody-mediated allograft rejection is a major cause of kidney transplant failure, with research focusing on identifying antibodies and optimizing therapies. New reagents and techniques have been used to measure MHC sensitization and isolate HLA-specific B cells from sensitized patients.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Urology & Nephrology
Aleksandar Senev, Evelyne Lerut, Maarten Coemans, Jasper Callemeyn, Hannah Charlotte Copley, Frans Claas, Priyanka Koshy, Vasilis Kosmoliaptsis, Dirk Kuypers, Ben Sprangers, Amaryllis Van Craenenbroeck, Elisabet Van Loon, Vicky Van Sandt, Marie-Paule Emonds, Maarten Naesens
Summary: The histology of antibody-mediated rejection after kidney transplantation can be observed in the absence of detectable donor-specific anti-HLA antibodies, and the degree of HLA mismatch is associated with the development of this phenotype.
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Urology & Nephrology
Baptiste Lamarthee, Carole Burger, Charlotte Leclaire, Emilie Lebraud, Aniela Zablocki, Lise Morin, Xavier Lebreton, Beatrice Charreau, Renaud Snanoudj, Soeli Charbonnier, Tifanie Blein, Melanie Hardy, Julien Zuber, Simon Satchell, Morgan Gallazzini, Fabiola Terzi, Christophe Legendre, Jean Luc Taupin, Marion Rabant, Claire Tinel, Dany Anglicheau
Summary: The study demonstrates that using human glomerular endothelial cells with all HLA antigens deleted as targets and recapitulating a large array of potential non-HLA antibodies in a single test can confirm the detrimental impact of non-HLA antibodies on microvascular inflammation and graft outcome after kidney transplantation, independent of HLA antibodies.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Article
Medicine, General & Internal
Florian Kaelble, Caner Suesal, Luiza Pego da Silva, Claudius Speer, Louise Benning, Christian Nusshag, Lien Pham, Hien Tran, Matthias Schaier, Claudia Sommerer, Joerg Beimler, Arianeb Mehrabi, Martin Zeier, Christian Morath
Summary: Living donor kidney transplant recipients with pre-existing sensitization can achieve good graft outcomes with desensitization protocols, comparable to standard-risk recipients. Adequate patient selection and close immunological monitoring are crucial to minimize rejection episodes and graft loss.
FRONTIERS IN MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Benjamin S. Mantell, Hector Cordero, Sarah B. See, Kevin J. Clerkin, Rodica Vasilescu, Charles C. Marboe, Yoshifumi Naka, Susan Restaino, Paolo C. Colombo, Linda J. Addonizio, Maryjane A. Farr, Emmanuel Zorn
Summary: The study found significant differences in gene expression profiles between patients with DSA and those without DSA, with signature genes involved in monocyte activation and response to interferon being expressed in the former. Additionally, there were substantial differences between the transcriptomic profiles of AMR defined by histopathological and immunopathological findings, with the latter associated with expression of mucin genes. However, no differential RNA expression was observed between patients with pAMR1i without DSA and those without AMR, as well as between patients with pAMR1h with DSA and pAMR2.
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2021)
Article
Cell Biology
Xavier Charmetant, Chien-Chia Chen, Sarah Hamada, David Goncalves, Carole Saison, Maud Rabeyrin, Marion Rabant, Jean-Paul Duong van Huyen, Alice Koenig, Virginie Mathias, Thomas Barba, Florence Lacaille, Jerome le Pavec, Olivier Brugiere, Jean-Luc Taupin, Lara Chalabreysse, Jean-Francois Mornex, Lionel Couzi, Stephanie Graff-Dubois, Raphal Jeger-Madiot, Alexy Tran-Dinh, Pierre Mordant, Helena Paidassi, Thierry Defrance, Emmanuel Morelon, Lionel Badet, Antonino Nicoletti, Valerie Dubois, Olivier Thaunat
Summary: Generation of antibodies against donor-specific MHC antigens after transplantation requires help from recipient's T cells, but our study shows that CD3e knockout recipient mice lacking T cells can still generate antibodies due to the presence of donor CD4+ T cells within the graft. This inverted direct pathway may also be operant in patients after transplantation.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Immunology
Marta Crespo, Laura Llinas-Mallol, Dolores Redondo-Pachon, Carrie Butler, Javier Gimeno, Maria Jose Perez-Saez, Carla Burballa, Anna Buxeda, Carlos Arias-Cabrales, Montserrat Folgueiras, Sara Sanz-Urena, Nicole M. Valenzuela, Elaine F. Reed, Julio Pascual
Summary: The relationship between HLA-DSA and ABMR in kidney transplant recipients is strong but imperfect. Pre-transplant HLA-DSA and AT(1)R-Ab are more common in ABMR, indicating their potential role in ABMR(h)DSA(pos) cases. HLA epitope mismatches are associated with ABMR(h)DSA(pos) cases, suggesting non-HLA factors may contribute to the development of ABMR.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Wei Liu, Zhong-Yu Kang, Zheng-Lu Wang, Dai-Hong Li
Summary: This study highlights the importance of specific DQa chain antibodies after renal transplantation.
TRANSPLANT IMMUNOLOGY
(2022)
Article
Immunology
Elisabet Van Loon, Baptiste Lamarthee, Thomas Barba, Sandra Claes, Maarten Coemans, Henriette de Loor, Marie-Paule Emonds, Priyanka Koshy, Dirk Kuypers, Paul Proost, Aleksandar Senev, Ben Sprangers, Claire Tinel, Olivier Thaunat, Amaryllis H. Van Craenenbroeck, Dominique Schols, Maarten Naesens
Summary: Through multiplex assay, we found that kidney transplant patients with donor-specific anti-human leukocyte antigen antibodies and histological rejection have increased levels of pro-inflammatory cytokines in blood. Even in patients without histological rejection, elevated pro-inflammatory cytokine levels can be observed. These findings challenge the concept of histology as the gold standard for identifying ongoing allo-immune activation after transplantation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Surgery
Aurore Prunevieille, Mohamed H. Babiker-Mohamed, Colleen Aslami, Bruno Gonzalez-Nolasco, Nuala Mooney, Gilles Benichou
Summary: Studies have shown that allogeneic exosomes can activate T cells in vivo and sensitize mice to alloantigens, but only when delivered in an inflammatory environment.
AMERICAN JOURNAL OF TRANSPLANTATION
(2021)
Review
Biochemistry & Molecular Biology
Nicolas Degauque, Alain Haziot, Sophie Brouard, Nuala Mooney
Summary: In the inflammation and infection caused by SARS-CoV-2, endothelial cells play a crucial role in regulating the recruitment of immune cells and interacting with monocytes, T cells, and B cells. Endothelial cells function as an integrative and active platform for immune responses, providing opportunities for therapeutic intervention.
Article
Immunology
Amy Rachael Cross, Julien Lion, Karine Poussin, Denis Glotz, Nuala Mooney
Summary: This study investigates the impact of inflammation on endothelial regulation of CD4(+)Treg cells. The findings suggest that high levels of inflammation can impair endothelial cell function and lead to inhibition of Treg differentiation. Blocking PD-L1 can partially restore Treg cell numbers.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Hematology
Sofiane Fodil, Marine Arnaud, Camille Vaganay, Alexandre Puissant, Etienne Lengline, Nuala Mooney, Raphael Itzykson, Lara Zafrani
Summary: The vascular microenvironment plays a crucial role in AML, with ECs and leukemic cells interacting to influence disease progression and complications.
Review
Biochemistry & Molecular Biology
Sara Assadiasl, Nuala Mooney, Mohammad Hossein Nicknam
Summary: Cytokines play crucial roles in autoimmune, allergic, and infectious diseases, as well as allograft rejection. Recent advances in novel anti-cytokine agents and gene therapy for immunomodulatory cytokines have shown significant improvements in managing dysregulated cytokine secretion and overexpression.
Article
Cell Biology
Thomas Bessy, Adrian Candelas, Benoit Souquet, Khansa Saadallah, Alexandre Schaeffer, Benoit Vianay, Damien Cuvelier, Samy Gobaa, Cecilia Nakid-Cordero, Julien Lion, Jean-Christophe Bories, Nuala Mooney, Thierry Jaffredo, Jerome Larghero, Laurent Blanchoin, Lionel Faivre, Stephane Brunet, Manuel Thery
Summary: The study reveals that the interaction between HSPCs and bone marrow stromal cells can induce polarization of HSPCs, leading to changes in cytoskeleton architecture, specifically the centrosome positioning. This polarization is specific and involves receptors ICAM, VCAM, and SDF1, with SDF1 being capable of independently inducing centrosome-microtubule network polarization.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Urology & Nephrology
Marine Arnaud, Maud Loiselle, Camille Vaganay, Stphanie Pons, Emmanuel Letavernier, Jordane Demonchy, Sofiane Fodil, Manal Nouacer, Sandrine Placier, Perrine Frere, Eden Arrii, Julien Lion, Nuala Mooney, Raphael Itzykson, Chakib Djediat, Alexandre Puissant, Lara Zafrani
Summary: This study provides new insights into the pathophysiology of TLS-induced AKI and suggests that extracellular histones may be a novel target for therapeutic intervention in TLS when endothelial dysfunction occurs.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Editorial Material
Medicine, General & Internal
Nuala Mooney
Article
Immunology
Guillaume Claisse, Magali Devriese, Julien Lion, Nicolas Maillard, Sophie Caillat-Zucman, Nuala Mooney, Jean Luc Taupin
Summary: This study experimentally validated that the assumption of underestimating the signal of anti-HLA antibodies in single antigen bead (SAB) assays when multiple beads share the targeted eplet is not true. Therefore, this phenomenon should no longer be considered as a significant risk factor during patient follow-up pre- or post-transplantation.
Article
Surgery
Julien Lion, Mathilde Le Maitre, Camille de Truchis, Jean-Luc Taupin, Karine Poussin, Alain Haziot, Edward Chong, Denis Glotz, Nuala Mooney
Summary: The microvascular endothelium of the renal transplant is the first site of graft interaction with the host immune system and is often injured in chronic Antibody Mediated Rejection (AMR). IL-6 plays a crucial role in EC immunogenicity, and blocking IL-6 can help improve related inflammatory responses.
CLINICAL TRANSPLANTATION
(2022)
Article
Gastroenterology & Hepatology
Tiong Y. Lim, Elena Perpinan, Maria-Carlota Londono, Rosa Miquel, Paula Ruiz, Ada S. Kurt, Elisavet Kodela, Amy R. Cross, Claudia Berlin, Joanna Hester, Fadi Issa, Abdel Douiri, Felix H. Volmer, Richard Taubert, Evangelia Williams, Anthony J. Demetris, Andrew Lesniak, Gilbert Bensimon, Juan Jose Lozano, Marc Martinez-Llordella, Tim Tree, Alberto Sanchez-Fueyo
Summary: This study investigated the role of low-dose IL-2 (LDIL-2) in maintaining liver allograft tolerance. The results showed that LDIL-2 expanded circulating regulatory T cells (Tregs) but failed to effectively suppress antigen-specific immune responses and promote the accumulation of intrahepatic Tregs. Furthermore, LDIL-2 induced a liver transcriptional response even before immunosuppression weaning. The study was terminated after the first 6 participants failed to reach the primary endpoint, requiring reinstitution of immunosuppression.
JOURNAL OF HEPATOLOGY
(2023)
Article
Immunology
Fabrice Cognasse, Hind Hamzeh-Cognasse, Anne-Claire Duchez, Natalia Shurko, Marie-Ange Eyraud, Charles-Antoine Arthaud, Amelie Prier, Marco Heestermans, Olivier Hequet, Brigitte Bonneaudeau, Sandrine Rochette-Eribon, Francoise Teyssier, Valerie Barlet-Excoffier, Patricia Chavarin, Dominique Legrand, Pascale Richard, Pascal Morel, Nuala Mooney, Pierre Tiberghien
Summary: Blood products in therapeutic transfusion contain biologically active constituents. This study investigated the effect of photochemical Pathogen Reduction Treatment (PRT) on inflammatory factors and endothelial cells in convalescent plasma. The results showed that most inflammatory soluble factors did not significantly change before and after PRT, but IL-8 concentrations decreased significantly and IL-18 concentrations increased. In addition, the release of IL-6 from cFFP was similar regardless of PRT treatment. Further research is needed to explore the physiological effects of IL-18 and IL-8, as well as the clinical relevance of PRT-treated convalescent plasma.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Joe N. Frost, Sarah K. Wideman, Alexandra E. Preston, Megan R. Teh, Zhichao Ai, Lihui Wang, Amy Cross, Natasha White, Yavuz Yazicioglu, Michael Bonadonna, Alexander J. Clarke, Andrew E. Armitage, Bruno Galy, Irina A. Udalova, Hal Drakesmith
Summary: Low plasma iron induced by hepcidin inhibits neutrophil production and alters their effector functions, while having no significant effect on other types of white blood cells. Antagonizing endogenous hepcidin can enhance neutrophil production during acute inflammation. These findings suggest that plasma iron plays a role in modulating the profile of innate immunity, with potential therapeutic implications.
Article
Surgery
Julien Lion, Mathilde Le Maitre, Camille de Truchis, Jean-Luc Taupin, Karine Poussin, Alain Haziot, Edward Chong, Denis Glotz, Nuala Mooney
Summary: The microvascular endothelium of the renal transplant is the first site of graft interaction with the host immune system and is often injured in chronic Antibody Mediated Rejection (AMR). IL-6 blockade is currently under investigation as a therapeutic target for AMR. This study examined the role of IL-6 in endothelial cell immunogenicity and found that IL-6 blockade reduced pro-inflammatory responses in EC.
CLINICAL TRANSPLANTATION
(2023)
Article
Medicine, Research & Experimental
Amy R. Cross, Carlos E. de Andrea, Maria Villalba-Esparza, Manuel F. Landecho, Lucia Cerundolo, Praveen Weeratunga, Rachel E. Etherington, Laura Denney, Graham Ogg, Ling -Pei Ho, Ian S. D. Roberts, Joanna Hester, Paul Klenerman, Ignacio Melero, Stephen N. Sansom, Fadi Issa
Summary: This study used spatial transcriptomics to explore the interactions between different immune and stromal cell populations in COVID-19-affected lung tissue. Through gene expression analysis of well-preserved lung samples from 3 patients, a common immune-cell signaling circuit involving cytotoxic lymphocytes and pro-inflammatory macrophages was identified in areas of severe lung damage. The expression of IFNG by cytotoxic lymphocytes was associated with the induction of chemokines, while TNF superfamily members (BAFF and TRAIL) were consistently upregulated in severely damaged areas. Validation of these findings in additional COVID-19 patient cohorts supports the potential use of this immune-mediated tissue pathology model for future therapeutic strategies.
