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Prophylaxis in hereditary angioedema: a United Kingdom Delphi consensus Clin. Exp. Immunol. (IF 4.6) Pub Date : 2024-03-08 Patrick F K Yong, Rachel Annals, Lavanya Diwakar, Shuayb Elkhalifa, Mark Gompels, Rashmi Jain, M Yousuf Karim, Sujoy Khan, Angela Metcalfe, Sadia Noorani, Cathal Steele, Sorena Kiani-Alikhan, Tomaz Garcez
Hereditary angioedema (HAE) is a rare inherited disorder causing recurrent of episodes of swelling that can be potentially life threatening. Treatment of HAE can be divided into on-demand treatment for swelling, and prophylaxis. The last UK consensus on HAE was in 2014 and since then, new medications for prophylaxis have been developed, with more drugs in the pipeline. International guidelines currently
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α2-antiplasmin is associated with macrophage activation and fibrin in a macrophage activation syndrome mouse model Clin. Exp. Immunol. (IF 4.6) Pub Date : 2024-03-07 Yosuke Kanno, Kinomi Toyama, Haruna Shibata, Osamu Matsuo, Kei-ichi Ozaki
Macrophage activation syndrome (MAS) is a life-threatening condition, characterized by cytopenia, multi-organ dysfunction, and coagulopathy associated with excessive activation of macrophages. In this study, we investigated that the roles of α2-antiplasmin (α2AP) in the progression of MAS using fulminant MAS mouse model induced by Toll-like receptor-9 (TLR-9) agonist (CpG) and d-galactosamine (DG)
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Quantifying Microglial Morphology: An Insight into Function Clin. Exp. Immunol. (IF 4.6) Pub Date : 2024-03-06 Tabitha R F Green, Rachel K Rowe
SUMMARY Microglia are specialized immune cells unique to the central nervous system (CNS). Microglia have a highly plastic morphology that changes rapidly in response to injury or infection. Qualitative and quantitative measurements of ever-changing microglial morphology are considered a cornerstone of many microglia-centric research studies. The distinctive morphological variations seen in microglia
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Conventional and unconventional T cell responses contribute to the prediction of clinical outcome and causative bacterial pathogen in sepsis patients Clin. Exp. Immunol. (IF 4.6) Pub Date : 2024-02-28 Ross J Burton, Loïc Raffray, Linda M Moet, Simone M Cuff, Daniel A White, Sarah E Baker, Bernhard Moser, Valerie B O’Donnell, Peter Ghazal, Matt P Morgan, Andreas Artemiou, Matthias Eberl
Sepsis is characterised by a dysfunctional host response to infection culminating in life-threatening organ failure that requires complex patient management and rapid intervention. Timely diagnosis of the underlying cause of sepsis is crucial, and identifying those at risk of complications and death is imperative for triaging treatment and resource allocation. Here, we explored the potential of explainable
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The balance between memory and regulatory cell populations in kidney transplant recipients with operational tolerance Clin. Exp. Immunol. (IF 4.6) Pub Date : 2024-02-23 Caner Süsal, Cristiam M Alvarez, Louise Benning, Volker Daniel, Martin Zeier, Matthias Schaier, Christian Morath, Claudius Speer
Donor-reactive memory cells represent a barrier to long-term kidney graft survival. A better understanding of regulatory mechanisms that counterbalance alloreactive memory responses may help to identify patients with operational tolerance. This prospective study investigated the equilibrium between memory T cell subsets and regulatory T or B cells (Tregs, Bregs) in peripheral blood of kidney transplant
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Chronic malaria exposure is associated with inhibitory markers on T cells that correlate with atypical memory and marginal zone-like B cells Clin. Exp. Immunol. (IF 4.6) Pub Date : 2024-02-22 Robert A Mitchell, Itziar Ubillos, Pilar Requena, Joseph J Campo, Maria Ome-Kaius, Sarah Hanieh, Alexandra Umbers, Paula Samol, Diana Barrios, Alfons Jiménez, Azucena Bardají, Ivo Mueller, Clara Menéndez, Stephen Rogerson, Carlota Dobaño, Gemma Moncunill
Chronic immune activation from persistent malaria infections can induce immunophenotypic changes associated with T cell exhaustion. However, associations between T and B cells during chronic exposure remain undefined. We analyzed peripheral blood mononuclear cells from malaria-exposed pregnant women from Papua New Guinea and Spanish malaria-naïve individuals using flow cytometry to profile T cell exhaustion
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Regulatory T cell frequency and function in acute myocardial infarction patients and its correlation with ventricular dysfunction Clin. Exp. Immunol. (IF 4.6) Pub Date : 2024-02-22 Elena Berenice Martínez-Shio, Sherell Marín-Jáuregui, Alma Celeste Rodríguez Ortega, Lesly Marsol Doníz Padilla, Roberto González-Amaro, Carlos David Escobedo-Uribe, Adriana Elizabeth Monsiváis-Urenda
A high percentage of patients with acute coronary syndrome develop heart failure due to the ischemic event. Regulatory T (Treg) cells are lymphocytes with suppressive capacity that control the immune response and include the conventional CD4+ CD25hi Foxp3+ cells and the CD4+ CD25var CD69+ LAP+ Foxp3- IL-10+ cells. No human follow-up studies focus on Treg cells’ behavior after infarction and their possible
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Altered CD226/TIGIT expressions were associated with activated NK phenotypes in primary anti-phospholipid syndrome and affected by IL-4/JAK pathway Clin. Exp. Immunol. (IF 4.6) Pub Date : 2024-02-22 Yan Long, Ke-jia Lu, Chang-sheng Xia, Jing-hong Feng, Wen-yi Li, Yin-ting Ma, Yuan-yuan Sun, Chun-hong Fan, Chun Li
Natural killer (NK) cells were reported to be involved in the pathogenesis of primary antiphospholipid syndrome (pAPS). Immunosuppressive receptor TIGIT and activating receptor CD226 are specifically expressed on NK cells with competitive functions. This study aims to investigate the expression diversities of CD226/TIGIT on NK subsets and their associations with NK subsets activation phenotypes and
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Splenectomy at Early stage of Autoimmune Arthritis Delayed Inflammatory Response and Reduced Joint Deterioration in Mice Clin. Exp. Immunol. (IF 4.6) Pub Date : 2024-02-16 Esam Khanfar, Katalin Olasz, Szonja Gál, Erzsébet Gajdócsi, Béla Kajtár, Tamás Kiss, Péter Balogh, Timea Berki, Ferenc Boldizsár
The spleen plays a role in innate- and adaptive immunity, and autoimmune diseases like rheumatoid arthritis (RA). We investigated the effect of splenectomy in early and moderate stages of autoimmune arthritis in a mouse model. To induce recombinant human G1-induced arthritis (GIA), BALB/c mice were immunized intraperitoneally three times in 4 weeks interval with the rhG1 antigen. Mice were splenectomized
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Albumin influences leucocyte FcRn expression in the early days of kidney transplantation Clin. Exp. Immunol. (IF 4.6) Pub Date : 2024-02-14 Pierre Boulard, Nicolas Azzopardi, Romain Levard, Jean-Marie Cornec, Juliette Lamamy, Bérénice Prieur, Marie-Véronique Demattei, Hervé Watier, Philippe Gatault, Valérie Gouilleux-Gruart
FcRn, a receptor originally known for its involvement in IgG and albumin transcytosis and recycling, is also important in the establishment of the innate and adaptive immune response. Dysregulation of the immune response has been associated with variations in FcRn expression, as observed in cancer. Recently, a link between autophagy and FcRn expression has been demonstrated. Knowing that autophagy
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Defining the cross-reactivity between peanut allergens Ara h 2 and Ara h 6 using monoclonal antibodies Clin. Exp. Immunol. (IF 4.6) Pub Date : 2024-02-12 Orlee Marini-Rapoport, Monica L Fernández-Quintero, Tarun Keswani, Guangning Zong, Jane Shim, Lars C Pedersen, Geoffrey A Mueller, Sarita U Patil
In peanut allergy, Arachis hypogaea 2 (Ara h 2) and Arachis hypogaea 6 (Ara h 6) are two clinically relevant peanut allergens with known structural and sequence homology and demonstrated cross-reactivity. We have previously utilized X-ray crystallography and epitope binning to define the epitopes on Ara h 2. We aimed to quantitatively characterize the cross-reactivity between Ara h 2 and Ara h 6 on
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Exposure to Gestational Diabetes Mellitus increases subclinical inflammation mediated in part by obesity Clin. Exp. Immunol. (IF 4.6) Pub Date : 2024-02-09 Andrea Musumeci, Colm John McElwain, Samprikta Manna, Fergus McCarthy, Cathal McCarthy
Gestational diabetes mellitus (GDM) is a frequent and serious complication of pregnancy, often associated with obesity. Metabolic dysfunction and metainflammation are evident in both obesity and GDM. In this cross-sectional study we aimed at defining the direct contribution of the immune system in GDM, across the main metabolic tissues, specifically focusing on elucidating the roles of obesity and
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Allogeneic NK cells induce the in vitro activation of monocyte-derived and conventional type-2 dendritic cells and trigger an inflammatory response under cancer-associated conditions Clin. Exp. Immunol. (IF 4.6) Pub Date : 2024-02-08 E C Toffoli, A A van Vliet, C Forbes, A J Arns, H W M Verheul, J Tuynman, H J van der Vliet, J Spanholtz, T D de Gruijl
Natural killer (NK) cells are innate lymphocytes capable to recognize and kill virus-infected and cancer cells. In the past years, the use of allogeneic NK cells as anti-cancer therapy gained interest due to their ability to induce graft-versus-cancer responses without causing graft-versus-host disease and multiple protocols have been developed to produce high numbers of activated NK cells. While the
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Increased expression of complement C3c, iC3b and cells containing CD11b or CD14 in experimentally induced psoriatic lesion Clin. Exp. Immunol. (IF 4.6) Pub Date : 2024-02-02 Dina Rahkola, Rauno J Harvima, Ilkka T Harvima
Psoriasis is a chronic inflammatory skin disease with a characteristic isomorphic reaction, i.e., the Köbner reaction, induced by slight epidermal trauma. In this study, the tape-stripping technique was used to induce the development of Köbner reaction in 18 subjects with psoriasis. Eight subjects developed the positive reaction. To study the early cellular changes, skin biopsies were taken at the
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Clinical and Experimental Treatment of Primary Humoral Immunodeficiencies Clin. Exp. Immunol. (IF 4.6) Pub Date : 2024-02-02 Anna Szaflarska, Marzena Lenart, Magdalena Rutkowska-Zapała, Maciej Siedlar
Summary Selective IgA deficiency (sIgAD) and Common Variable Immunodeficiency (CVID) and Transient Hypogammaglobulinemia of Infancy (THI) are the most frequent forms of primary antibody deficiencies. Difficulties in initial diagnosis, especially in the early childhood, the familiar occurrence of these diseases, as well as the possibility of progression to each other suggest common cellular and molecular
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The alteration of mucosal bile acid profile is associated with nerve growth factor expression in mast cells and bowel symptoms in diarrhea-predominant irritable bowel syndrome Clin. Exp. Immunol. (IF 4.6) Pub Date : 2024-01-30 Bi-Yu Wu, Ping Xu, Li Cheng, Qian-Qian Wang, Hong-Yi Qiu, Xiu-Juan Yan, Sheng-Liang Chen
Mucosal bile acid (BA) profile is still unestablished in diarrhea-predominant irritable bowel syndrome (IBS-D). The aim of this study was to explore colonic mucosal BAs and their associations with mucosal mast cell (MMC)-derived nerve growth factor (NGF) and bowel symptoms in IBS-D. Colonic mucosal biopsies from 36 IBS-D patients and 35 healthy controls (HCs) were obtained for targeted BA profiling
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Revolutionising immune research with organoid-based co-culture and chip systems Clin. Exp. Immunol. (IF 4.6) Pub Date : 2024-01-27 D Papp, T Korcsmaros, I Hautefort
The intertwined interactions various immune cells have with epithelial cells in our body require sophisticated experimental approaches to be studied. Due to the limitations of immortalised cell lines and animal models, there is an increasing demand for human in vitro model systems to investigate the microenvironment of immune cells in normal and in pathological conditions. Organoids, which are self-renewing
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Organoids as a tool to study the impact of heterogeneity in gastrointestinal epithelium on host-pathogen interactions Clin. Exp. Immunol. (IF 4.6) Pub Date : 2024-01-21 Mindaugas Paužuolis, Pilar Samperio Ventayol, Mastura Neyazi, Sina Bartfeld
Summary The epithelium of the gastrointestinal tract has been extensively characterized using advanced histological and RNA sequencing techniques, which has revealed great cellular diversity. Pathogens, such as viruses and bacteria, are highly adapted to their host and often exhibit not only species-specificity, but also a preference or tropism for specific gastrointestinal segments or even cell types
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PNAd-expressing vessels characterize the dermis of CD3+ T cell-mediated cutaneous diseases Clin. Exp. Immunol. (IF 4.6) Pub Date : 2024-01-16 Fatimah Mohammad Budair, Takashi Nomura, Hirata Masahiro, Kenji Kabashima
T-cell recruitment to skin tissues is essential for inflammation in different cutaneous diseases; however, the mechanisms by which these T cells access the skin remain unclear. High endothelial venules expressing peripheral node address in (PNAd), an L-selectin ligand, are located in secondary lymphoid organs and are responsible for increasing T-cell influx into the lymphoid tissues. They are also
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Role of inter-alpha-trypsin inhibitor heavy chain 4 and its citrullinated form in experimental arthritis murine models Clin. Exp. Immunol. (IF 4.6) Pub Date : 2024-01-08 Tamaki Iwai, Ayako Ohyama, Atsumu Osada, Taihei Nishiyama, Masaru Shimizu, Haruka Miki, Hiromitsu Asashima, Yuya Kondo, Hiroto Tsuboi, Seiya Mizuno, Satoru Takahashi, Akihito Ishigami, Isao Matsumoto
Inter α trypsin inhibitor heavy chain 4 (ITIH4) is a major protein in serum and reported to be up-regulated at the onset of rheumatoid arthritis (RA). Its citrullinated form, cit-ITIH4, is specifically found in serum and synovial fluid of patients with RA. However, the detailed function of ITIH4 in arthritis remains unknown. The aim of this study was to clarify the role of ITIH4 and its citrullinated
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FGL1 in plasma extracellular vesicles is correlated with clinical stage of lung adenocarcinoma and anti-PD-L1 response Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-12-26 Yuchen Zhang, Kunpeng Zhang, Haoyu Wen, Di Ge, Jie Gu, Chunyi Zhang
Fibrinogen-like protein-1 (FGL1) is confirmed a major ligand of lymphocyte activation gene-3 (LAG3) which could inhibit antigen-mediated T cell response and evade immune supervision. Although hepatocytes secrete large amounts of FGL1, its high expression also be detected in solid tumors such as lung cancer, leading to a poor efficacy of immune checkpoint inhibitors therapy. Here we reported that FGL1
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Shift in the B-cell subsets between children with type 1 diabetes and/or celiac disease Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-12-22 Andrea Tompa, Maria Faresjö
Our purpose was to characterize the pattern of B-cell subsets in children with a combined diagnosis of type 1 diabetes (T1D) and celiac disease (C) since children with single or double diagnosis of these autoimmune diseases may differ in peripheral B-cell subset phenotype patterns. B-cells were analyzed with flow cytometry for the expression of differentiation/maturation markers to identify transitional
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Gene expression analysis revealed downregulation of complement receptor 1 in clonal B cells in cold agglutinin disease Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-12-22 Agnieszka Małecka, Ingunn Østlie, Gunhild Trøen, Jędrzej Małecki, Jan Delabie, Anne Tierens, Ludvig A Munthe, Sigbjørn Berentsen, Geir E Tjønnfjord
Cold Agglutinin Disease (CAD) is a rare B-cell lymphoproliferative disorder of the bone marrow, manifested by autoimmune hemolytic anemia caused by binding of monoclonal IgM autoantibodies to the I antigen. Underlying genetic changes have previously been reported, but their impact on gene expression profile has been unknown. Here, we define differentially expressed genes in CAD B cells. To unravel
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Itaconate as a key regulator of respiratory disease Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-11-29 Christina Michalaki, Gesa J Albers, Adam J Byrne
Summary Macrophage activation results in the accumulation of endogenous metabolites capable of adopting immunomodulatory roles; one such bioactive metabolite is itaconate. After macrophage stimulation, the TCA-cycle intermediate cis-aconitate is converted to itaconate (by aconitate decarboxylase-1, ACOD1) in the mitochondrial matrix. Recent studies have highlighted the potential of targeting itaconate
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Immunological dynamic characteristics in AML predict the long-term outcomes and GVHD occurrences post-transplantation Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-11-15 Weiwei Wang, Haibo Li, Yukun Guo, Lihua Zhang, Wenli Jiang, Naisheng Zheng, Se Peng, Xiaolin Guan, Guang Fan, Lisong Shen
To investigate the relationship between immune dynamic and GVHD risk, 111 initial diagnostic AML patients were reviewed. The flow cytometry data of 12 major lymphocyte subsets in BM from 60 transplant patients at 4 different time points were analyzed. Additionally, 90 immune subsets in PB of 11 post-transplantation on day 100 were reviewed. Our results demonstrated that transplant patients had longer
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Gender-affirming hormone therapy and autoimmunity: new insights from a three-year follow-up study. Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-11-14 Matteo Marconi,Gloria Riitano,Alessandra Daphne Fisher,Carlotta Cocchetti,Maria Teresa Pagano,Antonella Capozzi,Agostina Longo,Sara D'Arienzo,Linda Vignozzi,Maurizio Sorice,Elena Ortona,Marina Pierdominici
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The CXCL10-CXCR3 axis plays an important role in Kawasaki Disease Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-11-12 Sho Hosaka, Kazuo Imagawa, Yusuke Yano, Lisheng Lin, Junko Shiono, Miho Takahashi-Igari, Hideki Hara, Daisuke Hayashi, Hironori Imai, Atsushi Morita, Hiroko Fukushima, Hidetoshi Takada
The precise pathogenesis of Kawasaki Disease remains unknown. In an attempt to elucidate the pathogenesis of KD through the analysis of acquired immunity, we comprehensively examined the immunophenotypic changes in immune cells such as lymphocytes and monocytes along with various cytokines, focusing on differences between pre- and post- treatment samples. We found high levels of CXCL9 and CXCL10 chemokines
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Plasma circulating microRNAs associated with blood-based immune markers: a population-based study. Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-11-09 Samantha Leonard,Irma Karabegović,M Arfan Ikram,Shahzad Ahmad,Mohsen Ghanbari
MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression and different immune-related pathways. There is great interest to identify miRNAs involved in immune cell development and function in order to elucidate the biological mechanisms underlying immune system, its regulation, and disease. In this study we aimed to investigate the association of circulating
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CD3 downregulation identifies high-avidity human CD8 T cells. Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-11-09 Genevieve T Clutton,Ann Marie K Weideman,Melissa A Mischell,Sallay Kallon,Shayla Z Conrad,Fiona R Shaw,Joanna Warren,Lin Lin,JoAnn D Kuruc,Yinyan Xu,Cynthia Gay,Paul M Armistead,Michael Hudgens,Nilu P Goonetilleke
CD8 T cells recognize infected and cancerous cells via their T cell receptor (TCR), which binds peptide-MHC complexes on the target cell. The affinity of the interaction between the TCR and peptide-MHC contributes to the antigen sensitivity, or functional avidity, of the CD8 T cell. In response to peptide-MHC stimulation, the TCR-CD3 complex and CD8 co-receptor are downmodulated. We quantified CD3
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Tuning the potency and selectivity of ImmTAC molecules by affinity modulation Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-11-06 Ian B Robertson, Rachel Mulvaney, Nele Dieckmann, Alessio Vantellini, Martina Canestraro, Francesca Amicarella, Ronan O’Dwyer, David K Cole, Stephen Harper, Omer Dushek, Peter Kirk
T cell engaging bispecifics have great clinical potential for the treatment of cancer and infectious diseases. The binding affinity and kinetics of a bispecific molecule for both target and T cell CD3 have substantial effects on potency and specificity, but the rules governing these relationships are not fully understood. Using ImmTAC (Immune mobilizing monoclonal TCRs Against Cancer) molecules as
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Transcriptome profiling of regulatory T cells from children with Transient Hypogammaglobulinemia of Infancy. Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-11-04 Magdalena Rutkowska-Zapała,Agnieszka Grabowska,Marzena Lenart,Anna Kluczewska,Anna Szaflarska,Krzysztof Kobylarz,Anna Pituch-Noworolska,Maciej Siedlar
Transient Hypogammaglobulinemia of Infancy (THI) is one of the most common forms of hypogammaglobulinemia in the early childhood. THI is usually associated with chronic, recurrent bacterial and viral infections, life-threatening in some cases, yet its pathogenesis is still largely unknown. Since our previous findings indicated the possible role of Treg cells in the pathomechanism of THI, the aim of
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Diagnostic significance of blood lymphocyte activation markers in pre-eclampsia Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-11-03 Almagul Kurmanova, Gulfairuz Urazbayeva, Aigul Terlikbayeva, Damilya Salimbaeva, Ardak Ayazbekov
The adaptive and innate immune system is important in both initiating and preventing functional disorders during pregnancy, one of which is pre-eclampsia. The research aims to conduct the comparative quantification of selected subpopulations of peripheral blood immunoregulatory cells in pregnant women with pre-eclampsia in the third trimester. The marker receptors CD4, CD8, CD95, CD25, CD27, and the
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Type 1 interferon auto-antibodies are elevated in patients with decompensated liver cirrhosis Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-11-02 Gordon Greville, Sinead Cremen, Shauna O’Neill, Sarah Azarian, Gareth Brady, William McCormack, Adam H Dyer, Nollaig M Bourke, Olivier Touzelet, David Courtney, Ultan F Power, Paul Dowling, Tom K Gallagher, Connor G G Bamford, Mark W Robinson
Patients with decompensated liver cirrhosis, in particular those classified as Childs-Pugh class C, are at increased risk of severe COVID-19 upon infection with SARS-CoV-2. The biological mechanisms underlying this are unknown. We aimed to examine the levels of serum intrinsic antiviral proteins as well as alterations in the innate antiviral immune response in patients with decompensated liver cirrhosis
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Regulatory T Cells in Inflamed Liver are Dysfunctional in Murine Primary Biliary Cholangitis Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-11-02 Chia-I Lin, Yu-Wen Wang, Chih-Yu Liu, Hung-Wen Chen, Pi-Hui Liang, Ya-Hui Chuang
Primary biliary cholangitis (PBC) is a chronic autoimmune disease characterized by immune-mediated destruction of intrahepatic small bile ducts. CD8 T cells play a critical role in biliary destruction. However, regulatory T cells (Tregs) have also been identified in the portal tracts of PBC patients. This study tested the hypothesis that hepatic Tregs in PBC were dysfunctional in suppressing immune
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Valganciclovir modulates the TNF axis molecules expression and CD4+ T cell subsets in disseminated Kaposi Sarcoma patients Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-10-31 Lucero A Ramon-Luing, Julio Flores-Gonzalez, Luis Angel García-Rojas, Beda Islas-Muñoz, Patricia Volkow-Fernández, Leslie Chavez-Galan
Valganciclovir (VGC) was used in a randomized clinical trial in patients with disseminated Kaposi Sarcoma (DKS/HIV) as add-on therapy to evaluate the proinflammatory axis tumor necrosis factor (TNF) and its receptors (TNFRs) in T cells. Two treatment schedules were used: an experimental regime (ER) and a conventional treatment (CT). Mononuclear cells from patients with DKS/HIV were obtained at baseline
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Cultured lymphocytes’ mitochondrial genome integrity is not altered by cladribine Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-10-20 Elina Järvinen, Fumi Suomi, James B Stewart, Dimitri Guala, Miko Valori, Lilja Jansson, Janne Nieminen, Thomas G McWilliams, Pentti J Tienari
Cladribine tablets are a treatment for multiple sclerosis with effects on lymphocytes, yet its mode of action has not been fully established. Here, we analyzed the effects of cladribine on mitochondrial DNA integrity in lymphocytes. We treated cultured human T-cell lines (CCRF-CEM and Jurkat) with varying concentrations of cladribine to mimic the slow cell depletion observed in treated patients. The
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Leucine-rich repeat kinase 2 promotes the development of experimental severe acute pancreatitis Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-10-17 Yasuo Otsuka, Akane Hara, Kosuke Minaga, Ikue Sekai, Masayuki Kurimoto, Yasuhiro Masuta, Ryutaro Takada, Tomoe Yoshikawa, Ken Kamata, Masatoshi Kudo, Tomohiro Watanabe
Translocation of gut bacteria into the pancreas promotes the development of severe acute pancreatitis (SAP). Recent clinical studies have also highlighted the association between fungal infections and SAP. The sensing of gut bacteria by pattern recognition receptors promotes the development of SAP via the production of proinflammatory cytokines; however, the mechanism by which gut fungi mediate SAP
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Plasma levels of mannan-binding lectin-associated serine proteases are increased in type 1 diabetes patients with insulin resistance Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-10-12 Noppadol Kietsiriroje, Georgia E Scott, Ramzi A Ajjan, Jan Brôz, Verena Schroeder, Matthew D Campbell
Activation of the lectin pathway of the complement system, as demonstrated by elevated levels of mannan-binding lectin proteins (MBL), contributes to vascular pathology in type 1 diabetes (T1D). Vascular complications are greatest in T1D individuals with concomitant insulin resistance (IR), however, whether IR amplifies activiation of the lectin pathway in T1D is unknown. We pooled pre-treatment data
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Autoantibodies to beta tubulin in autoimmune liver diseases - relation to pANCA and clinical relevance Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-10-12 Beate Preuß, Amelie Frank, Birgit Terjung, Ulrich Spengler, Christoph Berg, Reinhild Klein
There was evidence that pANCA (perinuclear antineutrophil cytoplasmic antibodies) in autoimmune liver diseases react with human beta-tubulin-5 (TBB5). Here we re-evaluate the specificity and clinical relevance of anti-TBB5 antibodies. Patients with untreated autoimmune hepatitis (AIH; n=53), AIH under immunosuppressive therapy (AIH-IS; n=125), primary sclerosing cholangitis (PSC; n=40), primary biliary
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Interleukin-11 and its eminent role in tissue fibrosis: A possible therapeutic target Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-09-19 Steven O’Reilly
Interleukin-11 is a cytokine from the IL-6 family of cytokines that includes IL-6 and OSM. Initially described for its role in platelet generation, it is now appreciated that this cytokine has multiple functions. Recently it has been found that IL-11 is critical in fibrosis in multiple different organ systems and systemically as in the autoimmune disease systemic sclerosis. Animal models of fibrosis
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Heterogeneity in RAG 1/2 Deficiency: 35 Cases From A Single Center Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-09-17 Betul Karaatmaca, Deniz Cagdas, Saliha Esenboga, Baran Erman, Cagman Tan, Tuba Turul Ozgur, Kaan Boztug, Mirjam Van Der Burg, Ozden Sanal, Ilhan Tezcan
Recombination activating genes (RAG) 1/2 deficiency leads to combined T/B cell deficiency with varying clinical presentations. This study aimed to define the clinical/laboratory spectrum of RAG1/2 deficiency. We retrospectively reviewed the clinical/laboratory data of 35 patients, grouped them as severe combined immunodeficiency (SCID), Omenn Syndrome (OS), and delayed-onset combined immunodeficiency
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Myelin oligodendrocyte glycoprotein antibody and N-methyl-d-aspartate receptor antibody overlapping syndrome: insights from the recent case reports Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-09-15 Bing-Qing Du, Qi-Lun Lai, Er-Chuang Li, Meng-Ting Cai, Gao-Li Fang, Chun-Hong Shen, Yin-Xi Zhang, Mei-Ping Ding
The overlapping of two or more types of neural autoantibodies in one patient has increasingly been documented in recent years. The coexistence of myelin oligodendrocyte glycoprotein (MOG) and N-methyl-d-aspartate receptor (NMDAR) antibodies is most common, which leads to a unique condition known as the MOG antibody and NMDAR antibody overlapping syndrome (MNOS). Here, we have reviewed the pathogenesis
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IL-21, Not IL-17A, Exacerbates Murine Primary Biliary Cholangitis Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-09-13 Chun-Wen Chan, Hung-Wen Chen, Yu-Wen Wang, Chia-I Lin, Ya-Hui Chuang
Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease caused by intrahepatic bile duct injuries, resulting in fibrosis, cirrhosis, and eventually liver failure. T helper (Th) 17 cells are proposed to involve in the pathogenesis of PBC. However, how and which Th17 cell-derived cytokines affect PBC remains unclear. In this study, we investigated the effects of Th17 effector cytokines
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Neutrophil extracellular traps are involved in the occurrence of interstitial lung disease in a murine experimental autoimmune myositis model Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-09-06 Ling Bai, Jiarui Zhu, Wenlan Ma, Feifei Li, Peipei Zhao, Sigong Zhang
The excessive formation of neutrophil extracellular traps (NETs) has been demonstrated to be a pathogenic mechanism of idiopathic inflammatory myopathy (IIM)-associated interstitial lung disease (ILD). This study aimed to answer whether an experimental autoimmune myositis (EAM) model can be used to study IIM-ILD and whether NETs participate in the development of EAM-ILD. An EAM mouse model was established
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Disease Activity in Chronic Inflammatory Demyelinating Polyneuropathy: Association Between Circulating B Cell Subsets, Cytokine Levels and Clinical Outcomes. Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-08-28 Ayse Nur Ozdag Acarli,Erdem Tuzun,Elif Sanli,Gizem Koral,Ece Akbayir,Arman Cakar,Nermin Gorkem Sirin,Aysun Soysal,Fikret Aysal,Hacer Durmus,Yesim Parman,Vuslat Yilmaz
OBJECTIVE To evaluate the relationship between immunological markers and clinical outcome measures in a mixed cohort of patients with typical CIDP and CIDP variants at different disease stages. METHODS Twenty-three typical, 16 multifocal and 5 distal CIDP patients were included. Twenty-five sex and age-matched healthy controls and 12 patients with Charcot-Marie-Tooth type 1A (CMT1A) disease served
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MAIT cells in bacterial infectious diseases: Heroes, villains, or both? Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-08-22 Sihong Wu, Xi Yang, Yongliang Lou, Xingxing Xiao
Due to the aggravation of bacterial drug resistance and the lag in the development of new antibiotics, it is crucial to develop novel therapeutic regimens for bacterial infectious diseases. Currently, immunotherapy is a promising regimen for the treatment of infectious diseases. Mucosal-associated invariant T (MAIT) cells, a subpopulation of innate-like T cells, are abundant in humans and can mount
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Difference in respiratory syncytial virus-specific Fc-mediated antibody effector functions between children and adults Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-08-22 Anke J Lakerveld, Anne T Gelderloos, Rutger M Schepp, Cornelis A M de Haan, Robert S van Binnendijk, Nynke Y Rots, Josine van Beek, Cécile A C M van Els, Puck B van Kasteren
Respiratory syncytial virus (RSV) infections are a major cause of bronchiolitis and pneumonia in infants and older adults, for which there is no known correlate of protection. Increasing evidence suggests that Fc-mediated antibody effector functions have an important role, but little is known about the development, heterogeneity, and durability of these functional responses. In light of future vaccine
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Female-specific enhancement of eosinophil recruitment and activation in a type 2 innate inflammation model in the lung Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-08-22 Rami Karkout, Véronique Gaudreault, Lydia Labrie, Haya Aldossary, Noelia Azalde Garcia, Jichuan Shan, Elizabeth D Fixman
A sex disparity in asthma prevalence and severity exists in humans. Multiple studies have highlighted the role for innate cells in shaping the adaptive immune system in chronic asthma. To explore the sex bias in the eosinophilic response, we delivered IL-33 to the lungs of mice and delineated the kinetics by which the inflammatory response was induced. Our data demonstrate that females recruited more
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A novel Nlrp3 knock-in mouse model with hyperactive inflammasome in development of lethal inflammation Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-08-18 Yongting Zhou, Xiyue Yang, Lei Zhu
NOD-like receptor family, pyrin domain-containing 3 (NLRP3) is a central protein contributing to human inflammatory disorders, including cryopyrin associated periodic syndrome and sepsis. However, the molecular mechanisms and functions of NLRP3 activation in various diseases remain unknow. Here, we generated gain-of-function knock-in mice associated with Muckle-Wells syndromes using the Cre-LoxP system
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IL-38 alleviates airway remodeling in chronic asthma via blocking the profibrotic effect of IL-36γ Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-08-17 Min Zhang, Jian-xia Zhou, Chu-qin Huang, Kang-ni Feng, Xiao-ling Zou, Jie-mei Cen, Ping Meng, Hong-tao Li, Tian-tuo Zhang
Airway remodeling is a major feature of asthma. Interleukin (IL)-36γ is significantly up-regulated and promotes airway hyperresponsiveness (AHR) in asthma, but its role in airway remodeling is unknown. Here, we aimed to investigate the role of IL-36γ in airway remodeling, and whether IL-38 can alleviate airway remodeling in chronic asthma by blocking the effects of IL-36γ. IL-36γ was quantified in
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IAPs and RIPK1 mediate LPS-induced cytokine production in healthy subjects and Crohn's disease. Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-08-16 Jakob Benedict Seidelin,Simone Jensen,Morten Hansen,Mariana Rodrigues de Carvalho Bronze,Delphine Cuchet-Lourenҫo,Sergey Nejentsev,Eric Charles LaCasse,Ole Haagen Nielsen
Innate immune activity fuels intestinal inflammation in Crohn's disease (CD), an inflammatory bowel disease (IBD). Identification and targeting of new molecular regulators of the innate activity are warranted to control the disease. Inhibitor of apoptosis proteins (IAPs) regulate both cell survival and inflammatory signaling. We investigated effects of IAP inhibition by second mitochondria-derived
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2B4 - A potential target in Staphylococcus aureus associated allergic inflammation. Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-08-16 Pratibha Gaur,Mansour Seaf,Nirit Trabelsi,Orly Marcu,Daria Gafarov,Ora Schueler-Furman,Ofer Mandelboim,Micha Ben-Zimra,Francesca Levi-Schaffer
Staphylococcus aureus (SA) and its exotoxins activate eosinophils (Eos) and mast cells (MCs) via CD48, a GPI-anchored receptor belonging to the Signaling Lymphocytes Activation Molecules (SLAM) family. 2B4 (CD244), an immuno-regulatory transmembrane receptor also belonging to the SLAM family, is the high affinity ligand for CD48. 2B4 is expressed on several leukocytes including NK cells, T cells, basophils
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Tissue-Resident Memory T Cell: Ontogenetic Cellular Mechanism and Clinical Translation Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-08-16 Haoran Xu, Runhong Zhou, Zhiwei Chen
Mounting evidence has indicated the essential role of tissue-resident memory T (TRM) cells for frontline protection against viral infection and for cancer immune surveillance 1. TRM cells are transcriptionally, phenotypically, and functionally distinct from circulating memory T (Tcirm) cells. It is necessary to understand the unique ontogenetic mechanism, migratory regulation, and biological function
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Surface protein and functional analyses identify CD4+CD39+ TCR αβ+ and activated TCR Vδ1+ cells with distinct pro-inflammatory functions in Crohn's Disease lesions Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-08-16 Jan Devan, Vladimir Nosi, Julian Spagnuolo, Andrew Chancellor, Aisha Beshirova, J Pedro Loureiro, Alessandro Vacchini, Jan Hendrik Niess, Raffaele Calogero, Lucia Mori, Gennaro De Libero, Petr Hruz
Crohn’s disease (CD) is a chronic immune-mediated disorder of the gastrointestinal tract. Extensive screening studies have revealed the accumulation of immune cell subsets with unique plasticity and immunoregulatory properties in patients with CD. We performed phenotypic and functional studies on inflamed and non-inflamed bioptic tissue to investigate the presence of distinct T cells in the intestinal
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Regulatory T cells in autoimmune primary adrenal insufficiency Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-08-11 Thea Sjøgren, Jan-Inge Bjune, Eystein S Husebye, Bergithe E Oftedal, Anette S B Wolff
Primary adrenal insufficiency (PAI) is most often caused by an autoimmune destruction of the adrenal cortex resulting in failure to produce cortisol and aldosterone. The aetiology is thought to be a combination of genetic and environmental risk factors, leading to breakdown of immunological tolerance. Regulatory T cells (Tregs) are deficient in many autoimmune disorders, but it is not known whether
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Soluble wild-type ACE2 molecules inhibit newer SARS-CoV-2 variants and are a potential antiviral strategy to mitigate disease severity in COVID-19 Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-08-11 Rohan Ameratunga, Emily Mears, Euphemia Leung, Russell Snell, See-Tarn Woon, William Kelton, Natalie Medlicott, Anthony Jordan, William Abbott, Richard Steele, William Rolleston, Hilary Longhurst, Klaus Lehnert
SARS-CoV-2, the virus responsible for COVID-19, has caused havoc around the world. While several COVID-19 vaccines and drugs have been authorised for use, these antiviral drugs remain beyond the reach of most low- and middle-income countries. Rapid viral evolution is reducing the efficacy of vaccines and monoclonal antibodies and contributing to deaths of some fully vaccinated persons. Others with
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Increased thromboinflammatory load in hereditary angioedema Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-08-10 Olav Rogde Gramstad, Camilla Schjalm, Tom Eirik Mollnes, Erik Waage Nielsen
C1 inhibitor (C1Inh) is a serine protease inhibitor involved in the kallikrein-kinin system, the complement system, the coagulation system and the fibrinolytic system. In addition to the plasma leakage observed in hereditary angioedema (HAE), C1Inh deficiency may also affect these systems, which are important for thrombosis and inflammation. The aim of this study was to investigate the thromboinflammatory
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Compartment-driven imprinting of intestinal CD4 T cells in inflammatory bowel disease and homeostasis Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-08-09 Lisanne Lutter, José J M ter Linde, Eelco C Brand, David P Hoytema van Konijnenburg, Britt Roosenboom, Carmen Horjus Talabur-Horje, Bas Oldenburg, Femke van Wijk
The mucosal immune system is implicated in the etiology and progression of inflammatory bowel diseases. The lamina propria and epithelium of the gut mucosa constitute two separate compartments, containing distinct T cell populations. Human CD4 T cell programming and regulation of lamina propria and epithelium CD4 T cells, especially during inflammation, remains incompletely understood. We performed
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Targeting T-cell integrins in autoimmune and inflammatory diseases Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-08-09 Aidan J Kelly, Aideen Long
The recruitment of T-cells to tissues and their retention there are essential processes in the pathogenesis of many autoimmune and inflammatory diseases. The mechanisms regulating these processes have become better understood over the past three decades and are now recognised to involve temporally and spatially specific interactions between cell adhesion molecules. These include integrins, which are
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Natural killer cells and innate lymphoid cells but not NKT cells are mature in their cytokine production at birth Clin. Exp. Immunol. (IF 4.6) Pub Date : 2023-08-09 Dawid Swieboda, Thomas F Rice, Yanping Guo, Simon Nadel, Ryan S Thwaites, Peter J M Openshaw, Beth Holder, Fiona J Culley
Early life is a time of increased susceptibility to infectious diseases and development of allergy. Innate lymphocytes are crucial components of the initiation and regulation of immune responses at mucosal surfaces, but functional differences in innate lymphocytes early in life are not fully described. We aimed to characterise the abundance and function of different innate lymphocyte cell populations