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Mitsuhiro Akiyama, Tsutomu Takeuchi
IgG4-related disease is a heterogeneous immune-mediated fibroinflammatory condition that can affect every single organ. This disease is more prevalent in the elderly (the mean age of patients is above 60 years) and the prevalence rate is estimated to be over 4.6 per 100,000 population. Before making a diagnosis, the exclusion of malignancies, lymphoma, anti-neutrophil cytoplasmic antibody-associated vasculitis, multicentric Castleman disease, and other mimickers is crucial for appropriate treatment. Broad management guidelines have been published emphasizing the need for prompt treatment and the use of glucocorticoids as first-line drug therapy for induction of remission...
March 15, 2018: Drugs & Aging
Aitor Nogales, Michael S Piepenbrink, Jiong Wang, Sandra Ortega, Madhubanti Basu, Christopher F Fucile, John J Treanor, Alexander F Rosenberg, Martin S Zand, Michael C Keefer, Luis Martinez-Sobrido, James J Kobie
Influenza's propensity for antigenic drift and shift, and to elicit predominantly strain specific antibodies (Abs) leaves humanity susceptible to waves of new strains with pandemic potential for which limited or no immunity may exist. Subsequently new clinical interventions are needed. To identify hemagglutinin (HA) epitopes that if targeted may confer universally protective humoral immunity, we examined plasmablasts from a subject that was immunized with the seasonal influenza inactivated vaccine, and isolated a human monoclonal Ab (mAb), KPF1...
March 12, 2018: Scientific Reports
Nina V Palkola, Sari H Pakkanen, Oskari Heikinheimo, Jussi M Kantele, Anu Kantele
Mucosal antibodies constitute the first line of adaptive immune defence against invaders in the female genital tract (FGT), yet the sequence of events leading to their production is surprisingly poorly characterized. We explored the induction of pathogen-specific antibody-secreting cells (ASC) as a response to an acute infection in the upper FGT. We recruited 12 patients undergoing surgery due to an upper FGT infection (7/12 blood culture positive, 5/12 negative) and six healthy controls. Pathogens were sampled during surgery and PBMC collected in the acute phase of the disease (days 7-10)...
March 2, 2018: Journal of Reproductive Immunology
Stefan D Dojcinov, Falko Fend, Leticia Quintanilla-Martinez
The contribution of Epstein-Barr virus (EBV) to the development of specific types of benign lymphoproliferations and malignant lymphomas has been extensively studied since the discovery of the virus over the last 50 years. The importance and better understanding of the EBV-associated lymphoproliferative disorders (LPD) of B, T or natural killer (NK) cell type has resulted in the recognition of new entities like EBV+ mucocutaneous ulcer or the addition of chronic active EBV (CAEBV) infection in the revised 2016 World Health Organization (WHO) lymphoma classification...
March 7, 2018: Pathogens
Chih-Hang Anthony Tang, Shiun Chang, Adrienne W Paton, James C Paton, Dmitry I Gabrilovich, Hidde L Ploegh, Juan R Del Valle, Chih-Chi Andrew Hu
To relieve endoplasmic reticulum (ER) stress, IRE1 splices XBP1 messenger RNA (mRNA) or engages regulated IRE1-dependent decay (RIDD) of other mRNAs. Upon XBP1 deficiency, IRE1 switches to perform RIDD. We examined IRE1 in XBP1-deficient B cells and discovered that IRE1 undergoes phosphorylation at S729. We generated an anti-phospho-S729 antibody to investigate such phosphorylation. Compared with pharmacological ER stress inducers or Toll-like receptor ligands, the bacterial subtilase cytotoxin has an unusual capability in causing rapid and strong phosphorylation at S729 and triggering B cells to express spliced XBP1...
March 6, 2018: Journal of Cell Biology
Stella Cosenza, Karine Toupet, Marie Maumus, Patricia Luz-Crawford, Olivier Blanc-Brude, Christian Jorgensen, Danièle Noël
Objectives: Mesenchymal stem cells (MSCs) release extracellular vesicles (EVs) that display a therapeutic effect in inflammatory disease models. Although MSCs can prevent arthritis, the role of MSCs-derived EVs has never been reported in rheumatoid arthritis. This prompted us to compare the function of exosomes (Exos) and microparticles (MPs) isolated from MSCs and investigate their immunomodulatory function in arthritis. Methods: MSCs-derived Exos and MPs were isolated by differential ultracentrifugation. Immunosuppressive effects of MPs or Exos were investigated on T and B lymphocytes in vitro and in the Delayed-Type Hypersensitivity (DTH) and Collagen-Induced Arthritis (CIA) models...
2018: Theranostics
Rongxin Wang, Ruiling Xie, Zongchang Song
Chronic hepatitis B virus (HBV) infection is a complex disease with dysregulations in the immune system. Follicular helper T (Tfh) cells are professional B helper cells that are crucial to the development of antibody responses and are involved in a variety of diseases. In this study, we examined the circulating Tfh cells in patients with chronic HBV infection. We observed that CD3+ CD4+ CXCR5+ circulating Tfh cells contained a CD25+ Foxp3+ Treg-like subset that was significantly enriched in patients with chronic HBV infections...
February 28, 2018: Experimental Cell Research
Ming Hu, Jose Trevino, Lijun Yang, Dengfeng Cao, Xiuli Liu, Jinping Lai
Epstein-Barr virus (EBV)-positive diffuse large B cell lymphoma (DLBCL) of the elderly is a rare subtype of B-cell neoplasms. Primary gastric EBV-positive DLBCL of the elderly with partial plasmablastic phenotype is extremely rare. Differentiation of EBV-positive DLBCL of the elderly with partial plasmablastic phenotype from true plasmablastic lymphoma (PBL) is difficult and very important from the therapeutic and prognostic point of view. Here we report a case of a 59-year-old man with upper gastrointestinal bleeding...
March 2018: In Vivo
Felipe Leite de Oliveira, Sofia Nascimento Dos Santos, Lauremilia Ricon, Thayse Pinheiro da Costa, Jonathas Xavier Pereira, Camila Brand, Marise Lopes Fermino, Roger Chammas, Emerson Soares Bernardes, Márcia Cury El-Cheikh
Galectin-3 (Gal-3) is a β-galactoside binding protein that controls cell-cell and cell-extracellular matrix interactions. In lymphoid organs, gal-3 inhibits B cell differentiation by mechanisms poorly understood. The B cell development is dependent on tissue organization and stromal cell signaling, including IL-7 and Notch pathways. Here, we investigate possible mechanisms that gal-3 interferes during B lymphocyte differentiation in the bone marrow (BM) and spleen. The BM of gal-3-deficient mice (Lgals3-/- mice) was evidenced by elevated numbers of B220+ CD19+ c-Kit+ IL-7R+ progenitor B cells...
February 22, 2018: Scientific Reports
Can Chen, Kuang Chen, Xilian Huang, Kaile Wang, Shenxian Qian
The current study presents the case of a 9-year-old Chinese boy who presented with eosinophilia and elevated serum levels of immunoglobulin G4 (IgG4). A bone marrow puncture identified an elevated eosinophil rate of 23% (normal range, <5%), which indicated eosinophilia. However, gene analysis, fluorescent in situ hybridization and other examinations, including bone marrow aspiration, blood routine, auto-antibody tests and parasitic and allergens screening, contradicted a diagnosis of secondary or clonal eosinophilia...
March 2018: Experimental and Therapeutic Medicine
Maddalena Migliavacca, Andrea Assanelli, Maurilio Ponzoni, Roberta Pajno, Federica Barzaghi, Fabio Giglio, Francesca Ferrua, Marta Frittoli, Immacolata Brigida, Francesca Dionisio, Roberto Nicoletti, Miriam Casiraghi, Maria Grazia Roncarolo, Claudio Doglioni, Jacopo Peccatori, Fabio Ciceri, Maria Pia Cicalese, Alessandro Aiuti
Adenosine deaminase-deficient severe combined immunodeficiency disease (ADA-SCID) is a primary immune deficiency characterized by mutations in the ADA gene resulting in accumulation of toxic compounds affecting multiple districts. Hematopoietic stem cell transplantation (HSCT) from a matched donor and hematopoietic stem cell gene therapy are the preferred options for definitive treatment. Enzyme replacement therapy (ERT) is used to manage the disease in the short term, while a decreased efficacy is reported in the medium-long term...
2018: Frontiers in Immunology
Paulina M Budzyńska, Minna K Kyläniemi, Olli Lassila, Kalle-Pekka Nera, Jukka Alinikula
Differentiation of B cells into antibody secreting cells (ASCs), plasmablasts and plasma cells, is regulated by a network of transcription factors. Within this network factors including PAX5 and BCL6 prevent ASC differentiation and maintain the B cell phenotype. In contrast, BLIMP-1 and high IRF4 expression promote plasma cell differentiation. BLIMP-1 is thought to induce immunoglobulin secretion whereas IRF4 is needed for the survival of ASCs. The role of IRF4 in the regulation of antibody secretion has remained controversial...
February 11, 2018: Scandinavian Journal of Immunology
Qingyu Cheng, Laleh Khodadadi, Adriano Taddeo, Jens Klotsche, Bimba F Hoyer, Andreas Radbruch, Falk Hiepe
Antibody-secreting cells (ASCs), including short-lived plasmablasts and long-lived memory plasma cells (LLPCs), contribute to autoimmune pathology. ASCs, particularly LLPCs, refractory to conventional immunosuppressive drugs pose a major therapeutic challenge. Since stromal cells expressing C-X-C motif chemokine-12 (CXCL12) organize survival niches for LLPCs in the bone marrow, we investigated the effects of CXCL12 and its ligand CXCR4 on ASCs in lupus mice (NZB/W). Fewer adoptively transferred splenic ASCs were retrieved from the bone marrow of recipient immunodeficient Rag1-/- mice when the ASCs were pre-treated with the CXCR4 blocker AMD3100...
February 10, 2018: European Journal of Immunology
Khalid Muhammad, Ronald Rudolf, Duong Anh Thuy Pham, Stefan Klein-Hessling, Katsuyoshi Takata, Nobuko Matsushita, Volker Ellenrieder, Eisaku Kondo, Edgar Serfling
In lymphocytes, immune receptor signals induce the rapid nuclear translocation of preformed cytosolic NFAT proteins. Along with co-stimulatory signals, persistent immune receptor signals lead to high levels of NFATc1/αA, a short NFATc1 isoform, in effector lymphocytes. Whereas NFATc1 is not expressed in plasma cells, in germinal centers numerous centrocytic B cells express nuclear NFATc1/αA. When overexpressed in chicken DT40 B cells or murine WEHI 231 B cells, NFATc1/αA suppressed their cell death induced by B cell receptor signals and affected the expression of genes controlling the germinal center reaction and plasma cell formation...
2018: Frontiers in Immunology
Chia-Hsin Ju, Lisa K Blum, Sarah Kongpachith, Nithya Lingampalli, Rong Mao, Petter Brodin, Cornelia L Dekker, Mark M Davis, William H Robinson
Seasonal influenza vaccines elicit antibody responses that can prevent infection, but their efficacy is reduced in the elderly. While a subset of elderly individuals can still mount sufficient vaccine-induced antibody responses, little is known about the properties of the vaccine-induced antibody repertoires in elderly as compared to young responders. To gain insights into the effects of aging on influenza vaccine-induced antibody responses, we used flow cytometry and a cell-barcoding method to sequence antibody heavy and light chain gene pairs expressed by individual blood plasmablasts generated in response to influenza vaccination in elderly (aged 70-89) and young (aged 20-29) responders...
February 2, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Ervin E Kara, Cameron R Bastow, Duncan R McKenzie, Carly E Gregor, Kevin A Fenix, Rachelle Babb, Todd S Norton, Dimitra Zotos, Lauren B Rodda, Jana R Hermes, Katherine Bourne, Derek S Gilchrist, Robert J Nibbs, Mohammed Alsharifi, Carola G Vinuesa, David M Tarlinton, Robert Brink, Geoffrey R Hill, Jason G Cyster, Iain Comerford, Shaun R McColl
Activated B cells can initially differentiate into three functionally distinct fates-early plasmablasts (PBs), germinal center (GC) B cells, or early memory B cells-by mechanisms that remain poorly understood. Here, we identify atypical chemokine receptor 4 (ACKR4), a decoy receptor that binds and degrades CCR7 ligands CCL19/CCL21, as a regulator of early activated B cell differentiation. By restricting initial access to splenic interfollicular zones (IFZs), ACKR4 limits the early proliferation of activated B cells, reducing the numbers available for subsequent differentiation...
January 31, 2018: Journal of Experimental Medicine
Panos Stathopoulos, Aditya Kumar, Jason A Vander Heiden, Elba Pascual-Goñi, Richard J Nowak, Kevin C O'Connor
Pathogenic autoantibodies to muscle-specific tyrosine kinase (MuSK) can be found in patients with myasthenia gravis (MG) who do not have detectable antibodies to the acetylcholine receptor. Although the autoantibody-mediated pathology is well understood, much remains to be learned about the cellular immunology that contributes to autoantibody production. To that end, our laboratory has investigated particular components associated with the cellular immunopathology of MuSK MG. First, we found that B cell tolerance defects contribute to the abnormal development of the naive repertoire, which indicates that dysregulation occurs before the production of autoantibodies...
January 2018: Annals of the New York Academy of Sciences
Ayako Sakakibara, Kei Kohno, Ahmed E Eladl, Teerada Klaisuwan, Eri Ishikawa, Yuka Suzuki, Satoko Shimada, Masato Nakaguro, Yoshie Shimoyama, Taishi Takahara, Seiichi Kato, Naoko Asano, Shigeo Nakamura, Akira Satou
AIMS: The programmed death 1 (PD1)/PD1 ligand (PD-L1) axis plays an important role in tumour cells escape from immune control. PD-L1 immunohistochemistry is a useful predictor of immunotherapy response, but is still not widely used in the diagnostic setting. Here we describe results using PD-L1 immunohistochemistry during routine diagnostics in lymphoma. METHODS AND RESULTS: Ninety-one lymphoproliferative disease cases sharing tumour and nonmalignant Hodgkin/Reed-Sternberg (HRS)-like cells with and without Epstein-Barr virus (EBV) association were investigated by immunohistochemistry for PD-L1 (clone SP142)...
January 30, 2018: Histopathology
Edward Bloch, Fiona Robinson
Plasmablastic lymphoma is an unusual and aggressive form of diffuse large B-cell lymphoma, which arises more commonly within the oronasal mucosa. It should be considered as a differential diagnosis for rapidly growing periorbital lesions, particularly in the context of HIV positivity.
January 2018: Clinical Case Reports
Karen M Haas, Kristen L Johnson, James P Phipps, Cardinal Do
CD22 (Siglec-2) is a critical regulator of B cell activation and survival. CD22-/- mice generate significantly impaired Ab responses to T cell-independent type 2 (TI-2) Ags, including haptenated Ficoll and pneumococcal polysaccharides, Ags that elicit poor T cell help and activate BCR signaling via multivalent epitope crosslinking. This has been proposed to be due to impaired marginal zone (MZ) B cell development/maintenance in CD22-/- mice. However, mice expressing a mutant form of CD22 unable to bind sialic acid ligands generated normal TI-2 Ab responses, despite significantly reduced MZ B cells...
January 26, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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