European Journal of Immunology最新文献_第4页

Liver type 1 innate lymphoid cells undergo apoptosis in murine models of macrophage activation syndrome and are dispensable for disease. 在巨噬细胞活化综合征小鼠模型中，肝脏1型先天性淋巴细胞会发生凋亡，对疾病来说是不可或缺的。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-09-30 DOI: 10.1002/eji.202451043

Amber De Visscher, Marte Vandeput, Jessica Vandenhaute, Bert Malengier-Devlies, Eline Bernaerts, Kourosh Ahmadzadeh, Jessica Filtjens, Tania Mitera, Nele Berghmans, Philippe E Van den Steen, Christin Friedrich, Georg Gasteiger, Carine Wouters, Patrick Matthys

{"title":"Liver type 1 innate lymphoid cells undergo apoptosis in murine models of macrophage activation syndrome and are dispensable for disease.","authors":"Amber De Visscher, Marte Vandeput, Jessica Vandenhaute, Bert Malengier-Devlies, Eline Bernaerts, Kourosh Ahmadzadeh, Jessica Filtjens, Tania Mitera, Nele Berghmans, Philippe E Van den Steen, Christin Friedrich, Georg Gasteiger, Carine Wouters, Patrick Matthys","doi":"10.1002/eji.202451043","DOIUrl":"https://doi.org/10.1002/eji.202451043","url":null,"abstract":"Macrophage activation syndrome (MAS) exemplifies a severe cytokine storm disorder with liver inflammation. In the liver, classical natural killer (cNK) cells and liver-resident type 1 innate lymphoid cells (ILC1s) dominate the ILC population. Thus far, research has primarily focused on the corresponding role of cNK cells. Considering the liver inflammation and cytokine storm in MAS, liver-resident ILC1s represent an interesting population to explore due to their rapid cytokine production upon environmental triggers. By utilizing a Toll-like receptor (TLR)9- and TLR3:4-triggered MAS model, we showed that ILC1s highly produce IFN-γ and TNF-α. However, activated ILC1s undergo apoptosis and are strongly reduced in numbers, while cNK cells resist inflammation-induced apoptosis. Signs of mitochondrial stress suggest that this ILC1 apoptosis may be driven by inflammation-induced mitochondrial impairment. To study whether early induction of highly cytokine-producing ILC1s influences MAS development, we used Hobit KO mice due to their paucity of liver ILC1s but unaffected cNK cell numbers. Nevertheless, neither the severity of MAS features nor the total inflammatory cytokine levels were affected in these Hobit KO mice, indicating that ILC1s are dispensable for MAS pathogenesis. Collectively, our data demonstrate that ILC1s undergo apoptosis during TLR-triggering and are dispensable for MAS pathogenesis.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e2451043"},"PeriodicalIF":4.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sphingosine-1-phosphate receptor type 4 is critically involved in the regulation of peritoneal B-1 cell trafficking and distribution in vivo. 鞘氨醇-1-磷酸受体4型在体内参与调节腹膜B-1细胞的贩运和分布。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-09-29 DOI: 10.1002/eji.202350882

Janik Riese, Annabel Kleinwort, Maurice Hannemann, Celine Hähnel, Stephan Kersting, Tobias Schulze

{"title":"Sphingosine-1-phosphate receptor type 4 is critically involved in the regulation of peritoneal B-1 cell trafficking and distribution in vivo.","authors":"Janik Riese, Annabel Kleinwort, Maurice Hannemann, Celine Hähnel, Stephan Kersting, Tobias Schulze","doi":"10.1002/eji.202350882","DOIUrl":"https://doi.org/10.1002/eji.202350882","url":null,"abstract":"B-1 cells are crucially involved in immune defense and regulation of inflammation and autoimmunity. B-1 cells are predominantly located in the peritoneal and pleural cavities, although body cavity B-1 cells recirculate systemically under steady-state conditions. The chemokines CXCL12 and CXCL13 have been identified as the main regulators of peritoneal B-cell trafficking. In mice deficient for sphingosine-1-phosphate receptor 4 (S1PR4), B-1a and B-1b cell numbers are reduced in the peritoneal cavity by an unknown mechanism. In this study, we show that S1PR4-mediated S1P signaling modifies the chemotactic response of peritoneal B cells to CXCL13 and CXCL12 in vitro. In vivo, S1PR4-mediated S1P signaling affects both immigration into and emigration from the peritoneal cavity. Long-term reconstitution experiments of scid mice with wt or s1pr4 -/- peritoneal B cells revealed a distinct distributional pattern in secondary lymphoid organs. As a functional consequence, both plasmatic and mucosal IgM levels, the main product of B-1a cells, are reduced in mice reconstituted with s1pr4 -/- peritoneal cells. In summary, our data identify S1PR4 as the second S1P receptor (besides S1PR1), which is critically involved in the regulation of peritoneal B-1 cell function.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e2350882"},"PeriodicalIF":4.5,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Innate immunity champions: The diverse functions of macrophages. 先天免疫冠军：巨噬细胞的多种功能

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-09-23 DOI: 10.1002/eji.202451139

Francesca Biscu, Anissa Zouzaf, Donatella Cicia, Clare Pridans, Gianluca Matteoli

{"title":"Innate immunity champions: The diverse functions of macrophages.","authors":"Francesca Biscu, Anissa Zouzaf, Donatella Cicia, Clare Pridans, Gianluca Matteoli","doi":"10.1002/eji.202451139","DOIUrl":"https://doi.org/10.1002/eji.202451139","url":null,"abstract":"Macrophages are instrumental in maintaining tissue homeostasis, modulating inflammation, and driving regeneration. The advent of omics techniques has led to the identification of numerous tissue-specific macrophage subtypes, thereby introducing the concept of the \"macrophage niche\". This paradigm underscores the ability of macrophages to adapt their functions based on environmental cues, such as tissue-specific signals. This adaptability is closely linked to their metabolic states, which are crucial for their function and role in health and disease. Macrophage metabolism is central to their ability to switch between proinflammatory and anti-inflammatory states. In this regard, environmental factors, including the extracellular matrix, cellular interactions, and microbial metabolites, profoundly influence macrophage behavior. Moreover, diet and gut microbiota significantly impact macrophage function, with nutrients and microbial metabolites influencing their activity and contributing to conditions like inflammatory bowel disease. Targeting specific macrophage functions and their metabolic processes is leading to the development of novel treatments for a range of chronic inflammatory conditions. The exploration of macrophage biology enriches our understanding of immune regulation and holds the promise of innovative approaches to managing diseases marked by inflammation and immune dysfunction, offering a frontier for scientific and clinical advancement.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e2451139"},"PeriodicalIF":4.5,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In vitro modulation of T cells in myasthenia gravis by low-dose IL-2 小剂量 IL-2 对肌无力 T 细胞的体外调节作用

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-09-17 DOI: 10.1002/eji.202451268

Merve Çebi, Arman Çakar, Hacer Durmuş, Onur Akan, Fikret Aysal, Yeşim Parman, Güher Saruhan-Direskeneli

{"title":"In vitro modulation of T cells in myasthenia gravis by low-dose IL-2","authors":"Merve Çebi, Arman Çakar, Hacer Durmuş, Onur Akan, Fikret Aysal, Yeşim Parman, Güher Saruhan-Direskeneli","doi":"10.1002/eji.202451268","DOIUrl":"10.1002/eji.202451268","url":null,"abstract":"Follicular helper (Tfh), peripheral helper (Tph), and regulatory (Treg) T cells are involved in myasthenia gravis (MG) pathogenesis, an autoimmune disorder arising from autoantibodies targeting neuromuscular junction proteins. This study explores the impact of low-dose IL-2 on Tfh, Tph, and Treg cells in vitro in MG. Acetylcholine-receptor antibody-positive MG (AChR-MG), muscle-specific kinase antibody-positive MG (MuSK-MG) patients, and healthy controls (HC) were studied. Blood cells were cultured with/without IL-2 and compared by the ratios of IL-2 stimulated/unstimulated cultures. In both AChR-MG and MuSK-MG patients, CD25+FoxP3+Tregs were lower, while CXCR5+PD-1+ or ICOS+Tfh and CXCR5−PD-1+ or ICOS+Tph cells were higher compared with HC. Among the MG group, the FoxP3+ Treg cells in AChR-MG patients were even lower compared with MuSK-MG patients. In vitro IL-2 stimulation increased Tregs in all groups while decreasing PD-1+/ICOS+Tfh and PD-1+/ICOS+Tph populations. The fold-increase ratio of Tregs and the fold-decrease ratio of PD-1+ or ICOS+Tfh and ICOS+Tph cells in AChR-MG and MuSK-MG patients were greater than in HCs. Low-dose IL-2 treatment may balance Tfh, Tph, and Treg cells in MG patients, offering a potential opportunity for disease modulation.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 11","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451268","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lipid nanoparticle-mediated RNA delivery for immune cell modulation. 脂质纳米粒子介导的 RNA 递送用于免疫细胞调节。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-09-16 DOI: 10.1002/eji.202451008

Emily H Kim, Sridatta V Teerdhala, Marshall S Padilla, Ryann A Joseph, Jacqueline J Li, Rebecca M Haley, Michael J Mitchell

引用次数: 0

Testosterone and estradiol reduce inflammation of human macrophages induced by anti-SARS-CoV-2 IgG. 睾酮和雌二醇可减少抗 SARS-CoV-2 IgG 诱导的人类巨噬细胞炎症。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-09-09 DOI: 10.1002/eji.202451226

Sona Allahverdiyeva, Chiara E Geyer, Jennifer Veth, Laura M de Vries, Steven W de Taeye, Marit J van Gils, Jeroen den Dunnen, Hung-Jen Chen

{"title":"Testosterone and estradiol reduce inflammation of human macrophages induced by anti-SARS-CoV-2 IgG.","authors":"Sona Allahverdiyeva, Chiara E Geyer, Jennifer Veth, Laura M de Vries, Steven W de Taeye, Marit J van Gils, Jeroen den Dunnen, Hung-Jen Chen","doi":"10.1002/eji.202451226","DOIUrl":"https://doi.org/10.1002/eji.202451226","url":null,"abstract":"COVID-19, the disease caused by SARS-CoV-2, particularly causes severe inflammatory disease in elderly, obese, and male patients. Since both aging and obesity are associated with decreased testosterone and estradiol expression, we hypothesized that decreased hormone levels contribute to excessive inflammation in the context of COVID-19. Previously, we and others have shown that hyperinflammation in severe COVID-19 patients is induced by the production of pathogenic anti-spike IgG antibodies that activate alveolar macrophages. Therefore, we developed an in vitro assay in which we stimulated human macrophages with viral stimuli, anti-spike IgG immune complexes, and different sex hormones. Treatment with levels of testosterone reflecting young adults led to a significant reduction in TNF and IFN-γ production by human macrophages. In addition, estradiol significantly attenuated the production of a very broad panel of cytokines, including TNF, IL-1β, IL-6, IL-10, and IFN-γ. Both testosterone and estradiol reduced the expression of Fc gamma receptors IIa and III, the two main receptors responsible for anti-spike IgG-induced inflammation. Combined, these findings indicate that sex hormones reduce the inflammatory response of human alveolar macrophages to specific COVID-19-associated stimuli, thereby providing a potential immunological mechanism for the development of severe COVID-19 in both older male and female patients.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e2451226"},"PeriodicalIF":4.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ThymoSpheres culture: A model to study human polyclonal unconventional T cells. 胸腺球培养：研究人类多克隆非常规 T 细胞的模型。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-09-09 DOI: 10.1002/eji.202451265

Lore Billiet, Hanne Jansen, Melissa Pille, Lena Boehme, Guillem Sanchez Sanchez, Laurenz De Cock, Glenn Goetgeluk, Eva Pascal, Stijn De Munter, Lucas Deseins, Joline Ingels, Thomas Michiels, Robrecht De Vos, Amin Zolfaghari, Niels Vandamme, Jana Roels, Tessa Kerre, Ruslan I Dmitriev, Tom Taghon, David Vermijlen, Bart Vandekerckhove

{"title":"ThymoSpheres culture: A model to study human polyclonal unconventional T cells.","authors":"Lore Billiet, Hanne Jansen, Melissa Pille, Lena Boehme, Guillem Sanchez Sanchez, Laurenz De Cock, Glenn Goetgeluk, Eva Pascal, Stijn De Munter, Lucas Deseins, Joline Ingels, Thomas Michiels, Robrecht De Vos, Amin Zolfaghari, Niels Vandamme, Jana Roels, Tessa Kerre, Ruslan I Dmitriev, Tom Taghon, David Vermijlen, Bart Vandekerckhove","doi":"10.1002/eji.202451265","DOIUrl":"https://doi.org/10.1002/eji.202451265","url":null,"abstract":"In vitro cultures remain crucial for studying the fundamental mechanisms of human T-cell development. Here, we introduce a novel in vitro cultivation system based on ThymoSpheres (TS): dense spheroids consisting of DLL4-expressing stromal cells and human hematopoietic precursor cells, in the absence of thymic epithelial cells. These spheroids are subsequently cultured at the air-liquid interphase. TS generate large numbers of mature T cells, are easy to manipulate, scalable, and can be repeatably sampled to monitor T-cell differentiation. The mature T cells generated from primary human hematopoietic precursor cells were extensively characterized using single-cell RNA and combined T-cell receptor (TCR) sequencing. These predominantly CD8α T cells exhibit transcriptional and TCR CDR3 characteristics similar to the recently described human polyclonal αβ unconventional T cell (UTC) lineage. This includes the expression of hallmark genes associated with agonist selection, such as IKZF2 (Helios), and the expression of various natural killer receptors. The TCR repertoire of these UTCs is polyclonal and enriched for CDR3-associated autoreactive features and early rearrangements of the TCR-α chain. In conclusion, TS cultures offer an intriguing platform to study the development of this human polyclonal UTC lineage and its inducing selection mechanisms.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e2451265"},"PeriodicalIF":4.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MicroRNA-146a deficiency enhances host protection against murine cytomegalovirus. 微RNA-146a缺乏可增强宿主对小鼠巨细胞病毒的保护。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-09-09 DOI: 10.1002/eji.202451173

Pamela Wong, Jeffrey W Leong, Hyogon Sohn, Lily Chang, Catherine R Keppel, Carly C Neal, Celia C Cubitt, Tony Yao, Molly P Keppel, Jennifer Tran, Allison Burdi, Kimberly Hwang, Leslie A Fogel, Timothy Schappe, Lynne Marsala, Melissa M Berrien-Elliott, Julia A Wagner, Stephanie E Schneider, Ryan P Sullivan, Jeanette T Pingel, Megan A Cooper, Anthony R French, Todd A Fehniger

{"title":"MicroRNA-146a deficiency enhances host protection against murine cytomegalovirus.","authors":"Pamela Wong, Jeffrey W Leong, Hyogon Sohn, Lily Chang, Catherine R Keppel, Carly C Neal, Celia C Cubitt, Tony Yao, Molly P Keppel, Jennifer Tran, Allison Burdi, Kimberly Hwang, Leslie A Fogel, Timothy Schappe, Lynne Marsala, Melissa M Berrien-Elliott, Julia A Wagner, Stephanie E Schneider, Ryan P Sullivan, Jeanette T Pingel, Megan A Cooper, Anthony R French, Todd A Fehniger","doi":"10.1002/eji.202451173","DOIUrl":"https://doi.org/10.1002/eji.202451173","url":null,"abstract":"Natural killer (NK) cells are innate lymphoid cells that protect a host from viral infections and malignancies. MicroRNA-146a (miR-146a) is an important regulator of immune function that is highly expressed in NK cells and is further upregulated during murine cytomegalovirus (MCMV) infection. Here we utilized mice with a global targeted deletion of miR-146a to understand its impact on the innate immune responses to MCMV infection. MiR-146a-/- mice were protected from lethal MCMV infection, which was intrinsic to the hematopoietic compartment based on bone marrow chimera experiments. NK cell depletion abrogated this protection, implicating NK cells as critical for the miR-146a-/- protection from MCMV. Surprisingly, NK cells from miR-146a-deficient mice were largely similar to control NK cells with respect to development, maturation, trafficking, and effector functions. However, miR-146a-/- mice had increased NK cell numbers and frequency of the most mature Stage IV (CD27-CD11b+) NK cells in the liver at baseline, enhanced STAT1 phosphorylation, and increased selective expansion of Ly49H+ NK cells and T cells during MCMV infection. This study demonstrates a critical role for miR-146a in the host response to MCMV, arising from mechanisms that include increased NK cell numbers and early T-cell expansion.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e2451173"},"PeriodicalIF":4.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Key actors in neuropathophysiology: The role of γδ T cells. 神经病理生理学中的关键角色：γδ T 细胞的作用

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-09-06 DOI: 10.1002/eji.202451055

Deniz Bulgur, Raquel Macedo Moura, Julie C Ribot

{"title":"Key actors in neuropathophysiology: The role of γδ T cells.","authors":"Deniz Bulgur, Raquel Macedo Moura, Julie C Ribot","doi":"10.1002/eji.202451055","DOIUrl":"https://doi.org/10.1002/eji.202451055","url":null,"abstract":"The neuroimmune axis has been the focus of many studies, with special emphasis on the interactions between the central nervous system and the different immune cell subsets. T cells are namely recognized to play a critical role due to their interaction with nerves, by secreting cytokines and neurotrophins, which regulate the development, function, and survival of neurons. In this context, γδ T cells are particularly relevant, as they colonize specific tissues, namely the meninges, and have a wide variety of complex functions that balance physiological systems. Notably, γδ T cells are not only key components for maintaining brain homeostasis but are also responsible for triggering or preventing inflammatory responses in various pathologies, including neurodegenerative diseases as well as neuropsychiatric and developmental disorders. Here, we provide an overview of the current state of the art on the contribution of γδ T cells in neuropathophysiology and delve into the molecular mechanisms behind it. We aim to shed light on γδ T cell functions in the central nervous system while highlighting upcoming challenges in the field and providing new clues for potential therapeutic strategies.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e2451055"},"PeriodicalIF":4.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bead-by-bead normalization of single antigen assays: A necessary step for accurate detection of weak anti-HLA antibodies 单抗原检测的逐珠归一化：准确检测弱抗 HLA 抗体的必要步骤。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-09-05 DOI: 10.1002/eji.202451181

Cédric Usureau, Romain Lhotte, Magali Devriese, Jérémy Siemowski, Lionel Gabet, Véronique Letort, Jean-Luc Taupin

{"title":"Bead-by-bead normalization of single antigen assays: A necessary step for accurate detection of weak anti-HLA antibodies","authors":"Cédric Usureau, Romain Lhotte, Magali Devriese, Jérémy Siemowski, Lionel Gabet, Véronique Letort, Jean-Luc Taupin","doi":"10.1002/eji.202451181","DOIUrl":"10.1002/eji.202451181","url":null,"abstract":"Ascertaining the presence of weakly positive anti-HLA donor-specific antibodies (DSA) in organ transplantation with multiplex single antigen beads assays may be challenging despite their high sensitivity due to technical variability issues. Through extensive datasets of Next-Generation Sequencing HLA typings and single antigen analyses, we reassessed the mean fluorescence intensity (MFI) positivity threshold of the assay to enhance accuracy. By showing that some beads were more prone to false positivity than others, we propose a nuanced approach that accounts for nonspecific intrinsic reactivities at the HLA antigen level, that is, on a bead-by-bead basis, as it enhances assay precision and reliability. This is substantiated by a comprehensive statistical analysis of MFI values and the implementation of the determination of a “Quantile Adjusted Threshold 500” (QAT500) value for each bead. Applied to DSA detection during patients’ follow-up, this approach discriminated better and earlier low-strength DSA that would later raise their MFI above the clinically relevant threshold of 3000. Moving from a subjective interpretation to a more objective and precise methodology allows for standardizing HLA antibody and DSA detection. The study emphasizes the need for further research with real clinical data to validate and refine this approach.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 11","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451181","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0