Jean‐Paul Duong Van Huyen

Hôpital Necker-Enfants Malades

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Alexandre Loupy

Paris Cardiovascular Research Center

Marion Rabant

Inserm

Patrick Bruneval

Hôpital Européen

Christophe Legendre

Université Paris Cité

Olivier Aubert

Inserm

Carmen Lefaucheur

Université Paris Cité

Xavier Jouven

Paris Cardiovascular Research Center

Denis Glotz

Metabolism and Renal Physiology

Srini V. Kaveri

Inserm

Pierre Isnard

Université Paris Cité

Cooperative Institutions

Inserm

640

Université Paris Cité

481

Assistance Publique – Hôpitaux de Paris

463

Sorbonne Université

249

Sorbonne Paris Cité

217

Centre National de la Recherche Scientifique

216

Hôpital Necker-Enfants Malades

200

Délégation Paris 5

174

Hôpital Européen Georges-Pompidou

107

Institut Necker Enfants Malades

105

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Comparative Study of the Sensitivity of Lymphoblastoid and Transformed Monocytic Cell Lines to the Cytotoxic Effects of Viscum album Extracts of Different Origin

Chemotherapy (2003)

Jean‐Paul Duong Van Huyen Sandrine Delignat Michel D. Kazatchkine Srini V. Kaveri

Viscum album (VA) preparations consist of aqueous extracts of V. album, the European mistletoe. VA extracts contain mistletoe lectins, which are members of the ribosome-inactivating protein type II family. VA preparations have cytotoxic and immunomodulatory properties. Cytotoxicity induced by VA extracts may differ greatly according to the origin of the preparation (host tree, fermented extract) and the cell type. This work was performed to assess the cytotoxicity of various VA preparations, i.e. VA Qu FrF, Qu Spez, M Spez and VA P, in lymphoblastoid and monocytic cell lines. VA Qu FrF, Qu Spez and M Spez induced dose-dependent cell death and inhibition of cell proliferation in lymphoblastoid T cell lines and in transformed monocytic lines. In contrast, the majority of B cell lines tested were resistant to cytotoxicity induced by VA extracts. While VA Qu FrF, Qu Spez and M Spez were potent inducers of cell death, extracts of VA P, derived from mistletoe plants growing on pine trees, failed to induce any cell death in any of the cell lines examined.

Viscum album

Loranthaceae

Lymphoblast

10.1159/000074530

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Citations (17)

Renal arcuate vein thrombosis–induced acute kidney injury: a rare multiple-Hit–mediated disease

Clinical Kidney Journal (2022)

Clara Pardinhas Rui M. Filipe Paul Vergnaud Mathilde Grapin Elsa Ferrière

Renal arcuate vein thrombosis (RAVT) is a rare and recently recognized cause of acute kidney injury (AKI) in young adults. However, the precise incidence and underlying pathophysiologic mechanisms leading to AKI in these patients remain elusive.This study included all patients who underwent a kidney biopsy over a 40-month period sent to the pathology department of Necker-Enfants Malades Hospital, with evidence of RAVT. We performed coagulation tests, genetic testing for thrombophilia, complete urine toxicologic screening and kidney metagenomic sequencing to identify an underlying cause of thrombosis.We report five pediatric cases of RAVT discovered on kidney biopsy performed in the setting of unexplained AKI. Investigations did not reveal an underlying cause of thrombosis but only a significant nonsteroidal anti-inflammatory drugs (NSAIDs) use was reported in 4/5 patients, supporting a potential link between NSAIDs use and RAVT. By performing metagenomic sequencing on kidney biopsy samples, we detected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in the kidney of one patient. These results suggest that systemic SARS-CoV-2 infection may also be a key contributing factor of renal thrombosis, particularly by inducing potential endothelial disruption.In conclusion, RAVT-induced AKI appears to be a multiple hit-mediated disease in which NSAIDs consumption and viral infection such as SARS-CoV-2 may be crucial contributing factors. These findings may have significant public health implications given the prevalence of NSAIDs use in the general population. Increased awareness and additional study of future cases may lead to a better understanding of this rare cause of AKI in children and young adults.

Renal vein thrombosis

Acute tubular necrosis

10.1093/ckj/sfac244

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Citations (4)

Diagnostic dilemma in a 3-year-old girl with acute nephritic syndrome and hematologic abnormalities: Questions

Pediatric Nephrology (2022)

Samantha Innocenti Silvia Bernardi Maud Prévot Antonin Saldmann Maud Tusseau

Girl

Nephritic syndrome

Nephrology

Hematologic disorders

10.1007/s00467-022-05733-9

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Citations (0)

Essai de classification des rejets en transplantation rénale

Encyclopédie médico-chirurgicale. Néphrologie (2016)

C. Legendre Alexandre Loupy Marion Rabant Olivier Aubert Lucile Amrouche

10.1016/s1762-0945(15)64246-2

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Pathologic classification of antibody-mediated rejection correlates with donor-specific antibodies and endothelial cell activation

The Journal of Heart and Lung Transplantation (2013)

Marion Tible Alexandre Loupy Déwi Vernerey Caroline Suberbielle T. Beuscart

Concomitant

Histology

10.1016/j.healun.2013.05.012

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Citations (59)

Establishing diagnostic criteria for mastocytosis in skin biopsies

Histopathology (2021)

Philippe Drabent Laura Polivka Julie Agopian Jean‐Paul Duong Van Huyen Pierre‐Alain Thiébaut

The diagnosis of mastocytosis in skin biopsies can be challenging - particularly in cases with very few mast cells. More diagnostic criteria are needed.We analyzed 103 skin biopsies from patients with mastocytosis and compared them with biopsies from inflammatory skin lesions and normal skin. Using CD117 immunostaining, we determined the mast cell distribution pattern, the percentage of mast cells in the inflammatory infiltrate, and the mast cell count per mm². We found that a sheet-like or subepidermal distribution of mast cells was specific for mastocytosis. The most significant feature was the percentage of mast cells and not the mast cell count. We found that a mast cell percentage above 40% was fully specific in both adults and children but lacked sensitivity, especially in adults. In children, all cases with a percentage below 40% harbored a number of mast cells above 90 per mm², allowing a straightforward diagnosis. In adults, the diagnosis was more challenging and cases with less than 40% of mast cells could be diagnosed on account of a number of mast cells above 40 per mm², with 88.5% sensitivity and 95.2% specificity. Additional signs might be useful in difficult cases. However, CD25 immunostaining was not useful.We confirmed that the criteria currently applied in the bone marrow were not appropriate for the skin. Accordingly, we developed an algorithm for the diagnosis of mastocytosis in skin biopsies with a high level of interrater reproducibility (mean kappa 0.8).

Cutaneous Mastocytosis

CD117

Tryptase

Immunostaining

Mast (botany)

Skin biopsy

10.1111/his.14573

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Citations (11)

The authors reply

Kidney International (2024)

Thibaut d’Izarny-Gargas Alexandre Karras Jean‐Paul Duong Van Huyen

Thrombotic microangiopathy

Nephrosclerosis

Myeloproliferative neoplasm

Microangiopathy

10.1016/j.kint.2024.01.007

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Citations (0)

WARS1, TYMP and GBP1 display a distinctive microcirculation pattern by immunohistochemistry during antibody-mediated rejection in kidney transplantation

Scientific Reports (2022)

Bertrand Chauveau Antoine Garric Sylvaine Di-Tommaso Anne‐Aurélie Raymond Jonathan Visentin

Abstract Antibody-mediated rejection (ABMR) is the leading cause of allograft failure in kidney transplantation. Defined by the Banff classification, its gold standard diagnosis remains a challenge, with limited inter-observer reproducibility of the histological scores and efficient immunomarker availability. We performed an immunohistochemical analysis of 3 interferon-related proteins, WARS1, TYMP and GBP1 in a cohort of kidney allograft biopsies including 17 ABMR cases and 37 other common graft injuries. Slides were interpreted, for an ABMR diagnosis, by four blinded nephropathologists and by a deep learning framework using convolutional neural networks. Pathologists identified a distinctive microcirculation staining pattern in ABMR with all three antibodies, displaying promising diagnostic performances and a substantial reproducibility. The deep learning analysis supported the microcirculation staining pattern and achieved similar diagnostic performance from internal validation, with a mean area under the receiver operating characteristic curve of 0.89 (± 0.02) for WARS1, 0.80 (± 0.04) for TYMP and 0.89 (± 0.04) for GBP1. The glomerulitis and peritubular capillaritis scores, the hallmarks of histological ABMR, were the most highly correlated Banff scores with the deep learning output, whatever the C4d status. These novel immunomarkers combined with a CNN framework could help mitigate current challenges in ABMR diagnosis and should be assessed in larger cohorts.

Gold standard (test)

10.1038/s41598-022-23078-z

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Citations (10)

Molecular Microscope Strategy to Improve Risk Stratification in Early Antibody-Mediated Kidney Allograft Rejection

Journal of the American Society of Nephrology (2014)

Alexandre Loupy Carmen Lefaucheur Déwi Vernerey J. Chang Luis Hidalgo

Antibody-mediated rejection (ABMR) is the leading cause of kidney allograft loss. We investigated whether the addition of gene expression measurements to conventional methods could serve as a molecular microscope to identify kidneys with ABMR that are at high risk for failure. We studied 939 consecutive kidney recipients at Necker Hospital (2004-2010; principal cohort) and 321 kidney recipients at Saint Louis Hospital (2006-2010; validation cohort) and assessed patients with ABMR in the first 1 year post-transplant. In addition to conventional features, we assessed microarray-based gene expression in transplant biopsy specimens using relevant molecular measurements: the ABMR Molecular Score and endothelial donor-specific antibody-selective transcript set. The main outcomes were kidney transplant loss and progression to chronic transplant injury. We identified 74 patients with ABMR in the principal cohort and 54 patients with ABMR in the validation cohort. Conventional features independently associated with failure were donor age and humoral histologic score (g+ptc+v+cg+C4d). Adjusting for conventional features, ABMR Molecular Score (hazard ratio [HR], 2.22; 95% confidence interval [95% CI], 1.37 to 3.58; P=0.001) and endothelial donor-specific antibody-selective transcripts (HR, 3.02; 95% CI, 1.00 to 9.16; P<0.05) independently associated with an increased risk of graft loss. The results were replicated in the independent validation group. Adding a gene expression assessment to a traditional risk model improved the stratification of patients at risk for graft failure (continuous net reclassification improvement, 1.01; 95% CI, 0.57 to 1.46; P<0.001; integrated discrimination improvement, 0.16; P<0.001). Compared with conventional assessment, the addition of gene expression measurement in kidney transplants with ABMR improves stratification of patients at high risk for graft loss.

10.1681/asn.2013111149

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Citations (132)

Duodenal gangliocytic paraganglioma with lymph node metastasis and an 8-year follow-up

European Journal of Gastroenterology & Hepatology (2011)

Maximilien Barret Gabriel Rahmi Jean‐Paul Duong Van Huyen Bruno Landi Christophe Cellier

Gangliocytic paraganglioma (GP) is a rare tumor, usually located in the second part of the duodenum. On pathological examination, GP is characterized by the association of the histological features of paragangliomas, ganglioneuromas, and carcinoid tumors. Classical clinical presentations are upper gastrointestinal bleeding and abdominal pain. Preoperative diagnosis is difficult because of the submucosal site of the tumor, with usually negative mucosal biopsies. Endoscopic ultrasound helps establish the diagnosis and allows lymph node staging, which will guide the choice of the treatment. If GPs usually follow a benign course, metastatic spread to regional lymph nodes treated by surgical resection alone has been reported. We report a case of GP with lymph node metastases treated by duodenopancreatectomy with long-term disease-free survival, suggesting that surgical resection is a reasonable approach for metastatic GPs.

10.1097/meg.0b013e32834dfdfa

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Citations (34)