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JOURNAL ARTICLE
Elina Alaterre, Sara Ovejero, Caroline Bret, Laure Dutrieux, Dassou Sika, Raul Fernandez Perez, Marion Espéli, Thierry Fest, Michel Cogné, José Ignacio Martín-Subero, Pierre Milpied, Giacomo Cavalli, Jerome Moreaux
Plasma cells (PC) are highly specialized cells representing the end stage of B cell differentiation. We have shown that PC differentiation can be reproduced in vitro using elaborate culture systems. The molecular changes occurring during PC differentiation are recapitulated in this in vitro differentiation model. However, a major challenge exists to decipher the spatiotemporal epigenetic and transcriptional programs that drives the early stages of PC differentiation. We combined single cell (sc) RNA-seq and single cell ATAC-seq to decipher the trajectories involved in PC differentiation...
April 21, 2024: Blood
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JOURNAL ARTICLE
Pablo Canales-Herrerias, Mathieu Uzzan, Akihiro Seki, Rafael S Czepielewski, Bram Verstockt, Alexandra E Livanos, Fiona Raso, Alexandra Dunn, Daniel Dai, Andrew Wang, Zainab Al-Taie, Jerome Martin, Thomas Laurent, Huaibin M Ko, Minami Tokuyama, Michael Tankelevich, Hadar Meringer, Francesca Cossarini, Divya Jha, Azra Krek, John D Paulsen, Matthew D Taylor, Mohammad Zuber Nakadar, Joshua Wong, Emma C Erlich, Rachel L Mintz, Emily J Onufer, Beth A Helmink, Keshav Sharma, Adam Rosenstein, Danielle Ganjian, Grace Chung, Travis Dawson, Julius Juarez, Vijay Yajnik, Andrea Cerutti, Jeremiah J Faith, Mayte Suarez-Farinas, Carmen Argmann, Francesca Petralia, Gwendalyn J Randolph, Alexandros D Polydorides, Andrea Reboldi, Jean-Frederic Colombel, Saurabh Mehandru
Vedolizumab (VDZ) is a first-line treatment in ulcerative colitis (UC) that targets the α4β7- mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) axis. To determine the mechanisms of action of VDZ, we examined five distinct cohorts of patients with UC. A decrease in naïve B and T cells in the intestines and gut-homing (β7+ ) plasmablasts in circulation of VDZ-treated patients suggested that VDZ targets gut-associated lymphoid tissue (GALT). Anti-α4β7 blockade in wild-type and photoconvertible (KikGR) mice confirmed a loss of GALT size and cellularity because of impaired cellular entry...
April 19, 2024: Science Immunology
#3
JOURNAL ARTICLE
Yun Wang, Xu Yuan, Ting Wang, Wei Wei, Shiji Wu, Hongyan Hou
Host immune dysfunction plays a crucial role in the onset, progression, and outcome of hemophagocytic lymphohistiocytosis (HLH). This study aimed to comprehensively evaluate the peripheral immune profiles in patients with newly diagnosed secondary hemophagocytic lymphohistiocytosis (sHLH), and explore their predictive value for patient prognosis. A total of 77 patients with sHLH were enrolled in this study, with 31 of them experiencing mortality. Flow cytometry was used to assess the percentages, absolute numbers, and phenotypes of lymphocyte subsets...
December 2024: Virulence
#4
JOURNAL ARTICLE
Martina Riganati, Federica Zotta, Annalisa Candino, Ester Conversano, Antonio Gargiulo, Marco Scarsella, Anna Lo Russo, Chiara Bettini, Francesco Emma, Marina Vivarelli, Manuela Colucci
INTRODUCTION: The clinical evolution of steroid-sensitive forms of pediatric idiopathic nephrotic syndrome (INS) is highly heterogeneous following the standard treatment with prednisone. To date, no prognostic marker has been identified to predict the severity of the disease course starting from the first episode. METHODS: In this monocentric prospective cohort study we set up a reproducible and standardized flow cytometry panel using two sample tubes (one for B-cell and one for T-cell subsets) to extensively characterized the lymphocyte repertoire of INS pediatric patients...
2024: Frontiers in Immunology
#5
JOURNAL ARTICLE
Luise Rupp, Ina Dietsche, Maximilian Kießler, Ulrich Sommer, Alexander Muckenhuber, Katja Steiger, Casper W F van Eijck, Leonard Richter, Rouzanna Istvanffy, Carsten Jäger, Helmut Friess, Casper H J van Eijck, Ihsan Ekin Demir, Carmen Mota Reyes, Marc Schmitz
Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at advanced stages and associated with early distant metastasis and poor survival. Besides clinical factors, the tumor microenvironment (TME) emerged as a crucial determinant of patient survival and therapy response in many tumors, including PDAC. Thus, the presence of tumor-infiltrating lymphocytes and the formation of tertiary lymphoid structures (TLS) is associated with longer survival in PDAC. Although neoadjuvant therapy (NeoTx) has improved the management of locally advanced tumors, detailed insight into its effect on various TME components is limited...
2024: Frontiers in Immunology
#6
JOURNAL ARTICLE
Omid Reza Zekavat, Yasaman Movahednezhad, Amin Shahsavani, Sezaneh Haghpanah, Negin Shokrgozar, Hossein Golmoghaddam, Mehdi Kalani, Mohammad Reza Bordbar, Nargess Arandi
BACKGROUND: Development of antibodies against infused Factor VIII (FVIII) or "inhibitors" represents a major challenge following FVIII replacement therapy in patients with hemophilia A (HA). Recent studies have shown that certain cellular compartments of the immune system contribute to the production of such antibodies. Herein, we determined the frequency of class-switched CD19+ IgD- CD27+ /non-class-switched CD19+ IgD+ CD27+ memory B cell subsets and CD19+ CD27hi CD38hi plasmablasts in patients with severe HA and their association with the development of inhibitors in these patients...
April 16, 2024: Blood Research
#7
JOURNAL ARTICLE
Ali Sepahi, Hsi-En Ho, Prapti Vyas, Benjamin Umiker, Katalin Kis-Toth, Dmitri Wiederschain, Lin Radigan, Charlotte Cunningham-Rundles
Common variable immunodeficiency (CVID) is an immune defect characterized by hypogammaglobulinemia and impaired development of B cells into plasma cells. As follicular helper T cells (TFH ) play a central role in humoral immunity, we examined TFH cells in CVID, and investigated whether an inducible T cell co-stimulator (ICOS) agonist, vopratelimab, could modulate TFH , B cell interactions and enhance immunoglobulin production. CVID subjects had decreased TFH17 and increased TFH1 subsets; this was associated with increased transitional B cells and decreased IgG+ B and IgD- IgM- CD27+ memory B cells...
April 13, 2024: Clinical Immunology: the Official Journal of the Clinical Immunology Society
#8
JOURNAL ARTICLE
Yi Xie, Huimei Chen, Vasuki Ranjani Chellamuthu, Ahmad Bin Mohamed Lajam, Salvatore Albani, Andrea Hsiu Ling Low, Enrico Petretto, Jacques Behmoaras
Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful technique for investigating biological heterogeneity at the single-cell level in human systems and model organisms. Recent advances in scRNA-seq have enabled the pooling of cells from multiple samples into single libraries, thereby increasing sample throughput while reducing technical batch effects, library preparation time, and the overall cost. However, a comparative analysis of scRNA-seq methods with and without sample multiplexing is lacking...
March 29, 2024: International Journal of Molecular Sciences
#9
Evelina Rogges, Sabrina Pelliccia, Camilla Savio, Gianluca Lopez, Irene Della Starza, Giacinto La Verde, Arianna Di Napoli
Human herpesvirus 8 (HHV8)-associated diseases include Kaposi sarcoma (KS), multicentric Castleman disease (MCD), germinotropic lymphoproliferative disorder (GLPD), Kaposi sarcoma inflammatory cytokine syndrome (KICS), HHV8-positive diffuse large B-cell lymphoma (HHV8+ DLBCL), primary effusion lymphoma (PEL), and extra-cavitary PEL (ECPEL). We report the case of a human immunodeficiency virus (HIV)-negative male treated for cutaneous KS, who developed generalized lymphadenopathy, hepatosplenomegaly, pleural and abdominal effusions, renal insufficiency, and pancytopenia...
March 28, 2024: International Journal of Molecular Sciences
#10
JOURNAL ARTICLE
Ting-Ting Zhang, Rene Yu-Hong Cheng, Andee R Ott, Noelle P Dahl, Emmaline R Suchland, Claire M Stoffers, Gregory D Asher, Deyin Hou, Christopher D Thouvenel, Tyler F Hill, David J Rawlings, Richard G James
Posttransplant lymphoproliferative disease (PTLD) is a major therapeutic challenge that has been difficult to study using human cells because of a lack of suitable models for mechanistic characterization. Here, we show that ex vivo-differentiated B cells isolated from a subset of healthy donors can elicit pathologies similar to PTLD when transferred into immunodeficient mice. The primary driver of PTLD-like pathologies were IgM-producing plasmablasts with Epstein-Barr virus (EBV) genomes that expressed genes commonly associated with EBV latency...
April 10, 2024: Science Translational Medicine
#11
JOURNAL ARTICLE
Matthias Bruhn, Maureen Obara, Abdus Salam, Bibiana Costa, Annett Ziegler, Inken Waltl, Andreas Pavlou, Markus Hoffmann, Theresa Graalmann, Stefan Pöhlmann, Axel Schambach, Ulrich Kalinke
COVID-19 induces re-circulating long-lived memory B cells (MBC) that, upon re-encounter with the pathogen, are induced to mount immunoglobulin responses. During convalescence, antibodies are subjected to affinity maturation, which enhances the antibody binding strength and generates new specificities that neutralize virus variants. Here, we performed a single-cell RNA sequencing analysis of spike-specific B cells from a SARS-CoV-2 convalescent subject. After COVID-19 vaccination, matured infection-induced MBC underwent recall and differentiated into plasmablasts...
April 9, 2024: European Journal of Immunology
#12
JOURNAL ARTICLE
Jolanta Smok-Kalwat, Paulina Mertowska, Izabela Korona-Głowniak, Sebastian Mertowski, Paulina Niedźwiedzka-Rystwej, Dominika Bębnowska, Krzysztof Gosik, Andrzej Stepulak, Stanisław Góźdź, Jacek Roliński, Zofia Górecka, Jan Siwiec, Ewelina Grywalska
Background: Non-small-cell lung cancer (NSCLC) is one of the most frequently diagnosed diseases among all types of lung cancer. Infectious diseases contribute to morbidity and mortality by delaying appropriate anti-cancer therapy in patients with NSCLC. Methods: The study aimed to evaluate the effectiveness of vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) in 288 newly diagnosed NSCLC patients. The analysis of the post-vaccination response was performed after vaccination by assessing the frequency of plasmablasts via flow cytometry and by assessing the concentration of specific anti-pneumococcal antibodies using enzyme-linked immunosorbent assays...
March 6, 2024: Journal of Clinical Medicine
#13
Hu Zeng, Xingxing Zhu, Yue Wu, Yanfeng Li, Xian Zhou, Jens Watzlawik, Yin Chen, Ariel Raybuck, Daniel Billadeau, Virginia Shapiro, Wolfdieter Springer, Sun Jie, Mark Boothby
During the humoral immune response, B cells undergo rapid metabolic reprogramming with a high demand for nutrients, which are vital to sustain the formation of the germinal centers (GCs). Rag-GTPases sense amino acid availability to modulate the mechanistic target of rapamycin complex 1 (mTORC1) pathway and suppress transcription factor EB (TFEB) and transcription factor enhancer 3 (TFE3), members of the microphthalmia (MiT/TFE) family of HLH-leucine zipper transcription factors. However, how Rag-GTPases coordinate amino acid sensing, mTORC1 activation, and TFEB/TFE3 activity in humoral immunity remains undefined...
March 29, 2024: Research Square
#14
JOURNAL ARTICLE
Ke Xu, Elisabeth Nacheva
A 71-year-old female with relapsed IgA lambda myeloma developed progressive cytopenia. The peripheral blood film showed 5% blastoid cells. Flow cytometry analysis was indicative of plasma cells. The bone marrow smear was packed with plasmablasts. Target CD138-cell FISH and molecular karyotyping identified a complex genome. NGS identified high-risk mutations. Bone marrow histology confirmed myeloma with no evidence of acute leukaemia. The patient was diagnosed with plasmablastic progression of myeloma and secondary PCL...
April 6, 2024: Journal of Hematopathology
#15
JOURNAL ARTICLE
Ida Lindeman, Lene S Høydahl, Asbjørn Christophersen, Louise F Risnes, Jørgen Jahnsen, Knut E A Lundin, Ludvig M Sollid, Rasmus Iversen
Autoantibodies against the enzyme transglutaminase 2 (TG2) are characteristic of celiac disease (CeD), and TG2-specific immunoglobulin (Ig) A plasma cells are abundant in gut biopsies of patients. Here, we describe the corresponding population of autoreactive B cells in blood. Circulating TG2-specific IgA cells are present in untreated patients on a gluten-containing diet but not in controls. They are clonally related to TG2-specific small intestinal plasma cells, and they express gut-homing molecules, indicating that they are plasma cell precursors...
April 4, 2024: Cell Reports
#16
Samuel W Kazer, Colette Matysiak Match, Erica M Langan, Marie-Angèle Messou, Thomas J LaSalle, Elise O'Leary, Jessica Marbourg, Katherine Naughton, Ulrich H von Andrian, Jose Ordovas-Montanes
The nasal mucosa is frequently the initial site of respiratory viral infection, replication, and transmission. Recent work has started to clarify the independent responses of epithelial, myeloid, and lymphoid cells to viral infection in the nasal mucosa, but their spatiotemporal coordination and relative contributions remain unclear. Furthermore, understanding whether and how primary infection shapes tissue-scale memory responses to secondary challenge is critical for the rational design of nasal-targeting therapeutics and vaccines...
March 18, 2024: bioRxiv
#17
JOURNAL ARTICLE
Alexey Koshkin, Ulysse Herbach, María Rodríguez Martínez, Olivier Gandrillon, Fabien Crauste
Germinal centers (GCs) are the key histological structures of the adaptive immune system, responsible for the development and selection of B cells producing high-affinity antibodies against antigens. Due to their level of complexity, unexpected malfunctioning may lead to a range of pathologies, including various malignant formations. One promising way to improve the understanding of malignant transformation is to study the underlying gene regulatory networks (GRNs) associated with cell development and differentiation...
2024: PloS One
#18
JOURNAL ARTICLE
Qing Luo, Qiuyun Xiao, Lu Zhang, Biqi Fu, Xue Li, Zikun Huang, Junming Li
It is well established that increased peripheral helper T cells (TPH) and follicular helper T cells (TFH) was found in systemic lupus erythematosus (SLE) patients. However, the expression patterns and immunomodulatory roles of TIGIT and PD1 on TPH/TFH in SLE are poorly understood. The expression patterns of TIGIT and PD1 on TPH and TFH cells were examined using flow cytometry and their expression patterns in SLE patients were then further evaluated for their correlation with auto-antibodies, disease activity and severity, B cell differentiation...
March 30, 2024: Heliyon
#19
JOURNAL ARTICLE
Rong-Guang Luo, Yi-Fan Wu, Hai-Wen Lu, Dong Weng, Jia-Yan Xu, Le-Le Wang, Li-Sha Zhang, Cai-Qi Zhao, Jian-Xiong Li, Yong Yu, Xin-Ming Jia, Jin-Fu Xu
INTRODUCTION: Patients with allergic bronchopulmonary aspergillosis (ABPA) suffer from repeated exacerbations. However, the involvement of T cell subsets remains unclear. METHODS: We enrolled ABPA patients, asthma patients and healthy controls. Th1, Th2, Th17, Treg and IL-21+ CD4+ T cells in total or sorted subsets of peripheral blood mononuclear cells (PBMCs) and ABPA Bronchoalveolar Lavage fluid (BALF) were analyzed by flow cytometry. RNA sequencing of subsets of CD4+ T cells were done in exacerbated ABPA patients and healthy controls...
March 21, 2024: European Respiratory Journal
#20
Maria Teresa Brito, Ana Filipa Amador, Ricardo Moço Coutinho, Ana Ribeiro, Jorge S Almeida
Multicentric Castleman disease (MCD) is a poorly understood, heterogeneous lymphoproliferative disorder with benign hyperplastic lymph nodes and systemic inflammatory symptoms. Human herpesvirus-8 (HHV-8) may be associated with MCD, whether or not the patient is infected with the human immunodeficiency virus (HIV). A 74-year-old man presented with anaemia, thrombocytopenia and bilateral axillary adenomegaly of unknown origin. The patient was admitted to the hospital two years ago with clinical signs of weight loss, asthenia, anorexia and a maculopapular rash on the trunk and back...
February 2024: Curēus
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