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Clinical and Experimental Immunology

Greg Hodge, Sandra Hodge, Phan Tien Nguyen, Aeneas Yeo, Parama Sarkar, Arash Badiei, C L Holmes-Liew, Paul N Reynolds, Mark Holmes
Immunosuppressive therapy fails to suppress the production of pro-inflammatory cytokines, particularly by CD8+T cells, in stable lung transplant recipients and those undergoing chronic rejection, suggesting that some patients may become relatively resistant to immunosuppressants such as glucocorticoids (GC). We have shown loss of GC receptor (GCR) from the CD8+ cells, and we hypothesized that the drug membrane efflux pump, p-glycoprotein-1 (Pgp), may also be involved in lymphocyte steroid resistance following lung transplant...
January 20, 2018: Clinical and Experimental Immunology
Trixy David, Stephanie Ling, Anne Barton
Immune-mediated inflammatory diseases (IMIDs) are characterised by dysregulation of the normal immune response, which leads to inflammation. Together, they account for a high disease burden in the population, given that they are usually chronic conditions with associated co-morbidities. Examples include systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease and type 1 diabetes. Since the advent of genome-wide association studies, evidence of considerable genetic overlap in the loci predisposing to a wide range of IMIDs has emerged...
January 12, 2018: Clinical and Experimental Immunology
Yuan Zhang, Song Wang, Haiying Dong, Xin Yi, Jinxue Zhang, Xueqin Liu, Ran Zhuang, Yong Ding
This study examined the expression of the inhibitory receptor, leukocyte-associated immunoglobulin (Ig)-like receptor-1 (LAIR-1) in fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA) patients to investigate its potential role in the modulation of inflammatory cytokines, metalloproteinases (MMPs), and invasiveness of synoviocytes. LAIR-1 expression in synovial tissues from RA patients, osteoarthritis patients, and healthy donors was analyzed by immunohistochemistry. The membrane-bound form (mLAIR-1) was detected by flow cytometry...
January 12, 2018: Clinical and Experimental Immunology
Kitty de Leur, Marian C Clahsen-van Groningen, Thierry P P van den Bosch, Gretchen N de Graav, Dennis A Hesselink, Janneke N Samsom, Carla C Baan, Karin Boer
BACKGROUND: We hypothesize that T cells such as IL-21+BCL6+ T follicular helper cells can regulate B cell mediated immunity within the allograft during acute T-cell mediated rejection, this process may feed chronic allograft rejection on long term. To investigate this mechanism we determined the presence and activation status of organized T and B cells in so-called ectopic lymphoid structures (ELSs) in different types of acute renal allograft rejection. METHODS: Biopsies showing the following primary diagnosis were included: acute/active antibody-mediated rejection, C4d+ (a/aABMR), acute T cell-mediated rejection grade I (aTCMRI), and acute T cell-mediated rejection grade II (aTCMRII)...
January 10, 2018: Clinical and Experimental Immunology
Stefano Alivernini, Barbara Tolusso, Gianfranco Ferraccioli, Elisa Gremese, Mariola Kurowska-Stolarska, Iain B McInnes
Acute inflammation is a complex and tightly regulated homeostatic process that includes leukocyte migration from the vasculature into tissues to eliminate the pathogen/injury, followed by a pro-resolving response promoting tissue repair. However, if inflammation is uncontrolled as in chronic diseases such as Rheumatoid Arthritis (RA) it leads to tissue damage and disability. Synovial tissue inflammation in RA patients is maintained by sustained activation of multiple inflammatory positive-feedback regulatory pathways in a variety of cells including myeloid cells...
January 8, 2018: Clinical and Experimental Immunology
Ahmed Nadeem, Naif O Al-Harbi, Sheikh F Ahmad, Khalid E Ibrahim, Nahid Siddiqui, Mohammed M Al-Harbi
Acute lung injury (ALI) is a heterogeneous disease with the hallmarks of alveolar capillary membrane injury, increased pulmonary edema and pulmonary inflammation. The commonest direct etiological factor for ALI is usually parenchymal lung infection or hemorrhage. Reactive oxygen species (ROS) generated by NADPH oxidase (NOX2) are thought to play an important role in the pathophysiology of ALI. Glucose-6-phosphate dehydrogenase (G6PD) plays an important role both in production of ROS as well as their removal through supply of NADPH...
December 25, 2017: Clinical and Experimental Immunology
Sinda Bigenzahn, Birgit Juergens, Benedikt Mahr, Johann Pratschke, Alfred Koenigsrainer, Thomas Becker, Dietmar Fuchs, Gerald Brandacher, Alexander Kainz, Ferdinand Muehlbacher, Thomas Wekerle
BACKGROUND: Belatacept is a second generation CTLA4Ig fusion protein approved for immunosuppression in renal transplant recipients. It was intentionally designed to interrupt costimulation via CD28 by binding to its ligands B7.1 and B7.2. Experimental evidence suggests a potential additional mechanism for CTLA4Ig compounds through binding to B7 molecules expressed on antigen presenting cells (APCs) and upregulation of indoleamine 2,3-dioxygenase (IDO), an immunomodulating enzyme that catalyzes the degradation of tryptophan to kynurenine and that downregulates T cell immunity...
December 22, 2017: Clinical and Experimental Immunology
Weiwei Wang, Zhenmeng Wang, Yanghua Qin, Gusheng Tang, Gang Cai, Yaoyang Liu, Jun Zhang, Peng Zhang, Qian Shen, Lisong Shen, Weifeng Yu
Documented reports about Th17 cells revealed that Th17 play a critical role in inflammation and autoimmunity diseases. However, the role of Th17 in cancer remains contradictory. The interplay between Th17 and tumor cells in the tumor microenvironment of PHC needs to be further explored and the relationship between Th17, Tregs and Bregs has not been completely defined. In this study, numerous experiments were undertaken to elucidate the interaction of Th17 and Treg/Breg cells involved in PHC. Our work demonstrated that an increased Th17 were detected in the peripheral circulation and in tumor tissues in PHC patients...
December 22, 2017: Clinical and Experimental Immunology
Javier Merayo-Chalico, Ana Barrera-Vargas, Guillermo Juárez-Vega, Jorge Alcocer-Varela, Antonio Arauz, Diana Gómez-Martín
SLE patients are susceptible to the development of posterior reversible encephalopathy syndrome (PRES). The main theory about the physiopathology of PRES suggests there is brain-blood barrier damage, which is associated with endothelial dysfunction, and characterized by vasogenic edema. However, current evidence regarding its physiopathogenic mechanisms is quite scant. The aim of this study was to analyze the expression of different serum cytokines, as well as VEGF and sCD40L, in patients with PRES/SLE and to compare them with levels in SLE patients without PRES and in healthy controls...
December 22, 2017: Clinical and Experimental Immunology
Akanksha Dixit, Babita Balakrishnan, Anjali A Karande
Glycodelin is an immunomodulator, indispensable for the maintenance of pregnancy in humans. The glycoprotein induces apoptosis in activated CD4+ T cells, monocytes and NK cells, and suppresses the activity of cytotoxic T cells, macrophages and dendritic cells. This study explores the immunosuppressive property of glycodelin for its possible use in preventing graft rejection. Because glycodelin is found only in certain primates, the hypothesis was investigated in an allograft nude mouse model. It is demonstrated that treatment of alloactivated mononuclear cells with glycodelin thwarts graft rejection...
December 22, 2017: Clinical and Experimental Immunology
Andrzej Górski, Ewa Jończyk-Matysiak, Marzanna Łusiak-Szelachowska, Beata Weber-Dąbrowska, Ryszard Międzybrodzki, Jan Borysowski
Autoimmune liver disease (ALD) poses a difficult medical challenge as there is a significant number of patients in whom current therapy offers questionable or no benefit yet its side effects may be serious including the development of malignancy. Bacterial viruses (phages) have been increasingly recognized as immunomodulators contributing to immune homeostasis and curbing inflammation. Accumulating data suggest that phages may be useful in immunotherapy of ALD. Phages have been shown to downregulate the expression and/or production and activity of factors associated with hepatic injury (reactive oxygen species, TLR4 activation, NF-kappaB activation, pro-inflammatory and pro-coagulant activities of platelets) and upregulate the expression and/or production of factors demonstrated as playing protective role (Il-10, Il-1 receptor antagonist)...
December 20, 2017: Clinical and Experimental Immunology
Thao Thi Do, Chatchai Phoomak, Voraratt Champattanachai, Atit Silsirivanit, Ponlatham Chaiyarit
Oral lichen planus (OLP) is considered a chronic inflammatory immune-mediated disease of the oral mucosa. Immunopathogenesis of OLP is thought to be associated with cell-mediated immune dysregulation. O-GlcNAcylation is a form of reversible glycosylation. It has been demonstrated that O-GlcNAcylation promoted NF-κB signaling. Activation of NF-кB can induce expression of NLRP3 inflammasome which is a large intracellular multiprotein complex involving an immune response. Dysregulated expression of the NLRP3 inflammasome was reported to be associated with autoinflammatory diseases...
December 16, 2017: Clinical and Experimental Immunology
Timm Hoeres, Martin Wilhelm, Manfred Smetak, Elisabeth Holzmann, Gundula Schulze-Tanzil, Josef Birkmann
Vascular endothelial growth factor (VEGF) is an important regulator of physiological and pathological angiogenesis. Beside malignant and stromal cells, local immune cells shape VEGF signaling in the tumor microenvironment. Aminobisphosphonates like zoledronic acid (Zol) are drugs known to inhibit osteoclast activity and bone resorption, but also have immunomodulatory and anti-tumor effects. These properties have previously been linked to the downregulation of VEGF and interference with tumor neo-angiogenesis...
December 13, 2017: Clinical and Experimental Immunology
Ann L Benko, Carl A McAloose, Patrice M Becker, Dale Wright, Teresa Sunyer, Yuka Imamura Kawasawa, Nancy J Olsen, William J Kovacs
Repository corticotropin injection (RCI, H.P Acthar® Gel) has been approved for use in the management of multiple autoimmune and inflammatory diseases for over a half-century, but its mechanism of action is not well understood. We used RNA -Seq methods to define RCI-regulated mRNAs in cultured human B cells under conditions of activation by IL4 and CD40 ligand. Following IL4/CD40L activation and RCI treatment we found up-regulation of 115 unique mRNA transcripts and downregulation of 80 unique mRNAs. The effect on these RNA levels was dose-dependent for RCI and was distinct from changes in mRNA expression induced by treatment with a potent synthetic glucocorticoid...
December 4, 2017: Clinical and Experimental Immunology
Melanie R Neeland, Wei Shi, Catherine Collignon, Els N T Meeusen, Arnaud M Didierlaurent, Michael J de Veer
The liposome-based Adjuvant System AS01 is under evaluation for use in several vaccines in clinical development. We have previously shown that AS01 injected with hepatitis B surface antigen (HBsAg) induces a distinct cellular signature within the draining lymphatics that enhances local lymphocyte recruitment and antigen-specific humoral immunity. Here, we show that AS01-induced neutrophil recruitment is associated with increased expression of CD14 and enhanced antigen uptake capacity in neutrophils from both afferent and efferent lymphatic compartments in the first 48h after vaccination...
December 1, 2017: Clinical and Experimental Immunology
Batia Kaplan, Sizilia Golderman, Esther Ganelin-Cohen, Alla Miniovitch, Eitan Korf, Ilan Ben-Zvi, Avi Livneh, Shlomo Flechter
A new procedure was developed and applied to study immunoglobulin free light chains (FLC) in saliva of healthy subjects and patients with multiple sclerosis (MS). The procedure was based on a Western blot analysis for detection and semiquantitative evaluation of monomeric and dimeric FLCs. The FLC indices accounting for the total FLC levels and for the monomer/dimer ratios of κ and λ FLC were calculated, and the cut-off values of the FLC indices were determined to distinguish healthy state from MS disease...
November 30, 2017: Clinical and Experimental Immunology
Mehrdad Pazhouhandeh, Mohammad-Ali Sahraian, Seyed Davar Siadat, Abolfazl Fateh, Farzam Vaziri, Fatemeh Tabrizi, Faezeh Ajorloo, Arash Keshavarzi Arshadi, Elnaz Fatemi, Somaye Piri Gavgani, Fereidoun Mahboudi, Fatemeh Rahimi Jamnani
Identification of autoimmune processes and introduction of new autoantigens involved in the pathogenesis of multiple sclerosis (MS) can be helpful in the design of new drugs to prevent unresponsiveness and side effects in patients. To find significant changes, we evaluated the autoantibody repertoires in newly diagnosed relapsing-remitting MS patients (NDP) and those receiving disease modifying therapy (RP). Through a random peptide phage library, a panel of NDP- and RP-specific peptides was identified, producing two protein datasets visualized using Gephi, based on protein-protein interactions in the STRING database...
November 30, 2017: Clinical and Experimental Immunology
Elena Cerrillo, Inés Moret, Marisa Iborra, David Ramos, Enrique Busó, Luis Tortosa, Esteban Sáez-González, Pilar Nos, Belén Beltrán
BACKGROUND: An impaired expression of α-defensins (α-Defs) in the ileal mucosa and, conversely, increased levels in plasma, have been reported in Crohn's disease (CD). However, the specificity and correlation of these findings with the degree of inflammation are unclear. We aimed to characterize the concentration and utility of ileal and plasma α-Defs in CD and to analyze a potential epigenetic mechanism of α-Def expression. METHODS: Peripheral blood samples and ileal biopsies were obtained from patients at disease onset (aCD), from those who achieved remission (iCD), and from 2 control groups (healthy controls and non-CD-etiology ileitis patients)...
November 28, 2017: Clinical and Experimental Immunology
Brisse Ellen, Imbrechts Maya, Mitera Tania, Vandenhaute Jessica, Berghmans Nele, Boon Louis, Wouters H Carine, Snoeck Robert, Andrei Graciela, Matthys Patrick
Hemophagocytic lymphohistiocytosis (HLH) constitutes a spectrum of immunological disorders characterized by uncontrolled immune activation and key symptoms such as fever, splenomegaly, pancytopenia, hemophagocytosis, hyperferritinemia and hepatitis. In genetic or primary HLH, hyperactivated CD8+ T cells are the main drivers of pathology. However, in acquired, secondary HLH, the role of lymphocytes remains vague. In the present study the involvement of lymphocytes in the pathogenesis of a cytomegalovirus-induced model of secondary HLH was explored...
November 27, 2017: Clinical and Experimental Immunology
Ying Sun, Daogong Zhang, Gaoying Sun, Yafeng Lv, Yawei Li, Xiaofei Li, Yongdong Song, Jianfeng Li, Zhaomin Fan, Haibo Wang
To date, the pathogenesis of Meniere's disease (MD) remains unclear. This study aims to investigate the possible relationship between potential immune system related genes and sporadic Meniere's disease. The whole RNA-sequencing (RNA-seq) technology was used to analyze the transcriptome of peripheral blood mononuclear cells of 3 MD patients and 3 control individuals. Of 366 differentially expressed genes (DEGs), 154 genes were up-regulated and 212 genes were down-regulated (|log2Foldchange| >1 and p <0...
November 22, 2017: Clinical and Experimental Immunology
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