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Clinical and Experimental Immunology

Rianne P Gorter, Erik Nutma, Marie-Christina Jahreiβ, Jenny C de Jonge, Roy Quinlan, Paul van der Valk, Johannes M van Noort, Wia Baron, Sandra Amor
AIMS: Multiple sclerosis (MS) is a chronic neurodegenerative disease characterised by demyelination, inflammation and neurodegeneration throughout the central nervous system. Although spinal cord pathology is an important factor contributing to disease progression, few studies have examined MS lesions in the spinal cord and how they differ from brain lesions. Here we have compared brain and spinal cord white and grey matter from MS and control tissues focussing on small heat shock proteins (HSPB) and HSP16...
July 17, 2018: Clinical and Experimental Immunology
Ciputra Adijaya Hartana, Emma Ahlén Bergman, Augusta Broomé, Sofia Berglund, Markus Johansson, Farhood Alamdari, Tomasz Jakubczyk, Ylva Huge, Firas Aljabery, Karin Palmqvist, Benny Holmström, Hans Glise, Katrine Riklund, Amir Sherif, Ola Winqvist
Tissue-resident memory T (TRM ) cells are CD8+ T lymphocytes that reside in the tissues, including tumours. This T cell subset possesses a magnitude of cytotoxicity, but their epigenetic regulation has not been studied. Here, we investigate the impact of perforin DNA methylation in TRM cells and correlate it with their functional potentials. 53 urothelial urinary bladder cancer (UBC) patients were prospectively recruited. The DNA methylation status of the perforin gene (PRF1) locus in TRM cells was investigated by pyrosequencing...
July 15, 2018: Clinical and Experimental Immunology
Y Eiraku, H Terunuma, M Yagi, X Deng, Andrew J Nicol, M Nieda
The finding that dendritic cells (DCs) orchestrate innate and adaptive immune responses has stimulated research on harnessing DCs for developing more effective vaccines for DC therapy. The expression of cytomegalovirus (CMV) antigens in glioblastoma multiforme (GBM) presents a unique opportunity to target these viral proteins for tumor immunotherapy. Here, we demonstrate that Vγ9γδT cells, innate immune cells activated by zoledronate (Z), and Vα24NKT cells, innate/adaptive immune cells activated by α-galactosylceramide (G) can link innate and adaptive immunities through cross talk with IFN-DCs from patients with GBM and healthy donors in a way that can amplify the activation and proliferation of CMVpp65-specific CD8+T cells...
July 15, 2018: Clinical and Experimental Immunology
Fulvia Ceccarelli, Germano Orrù, Andrea Pilloni, Izabella Bartosiewicz, Carlo Perricone, Emilio Martino, Ramona Lucchetti, Sara Fais, Marta Vomero, Marta Olivieri, Manuela di Franco, Roberta Priori, Valeria Riccieri, Rossana Scrivo, Yehuda Shoenfeld, Cristiano Alessandri, Fabrizio Conti, Antonella Polimeni, Guido Valesini
OBJECTIVE: Several evidences suggested a link between human microbiome and Rheumatoid Arthritis (RA) development. Porphyromonas gingivalis (P. gingivalis) seems involved in RA initiation and progression, as supported by the high occurrence of periodontitis. In this case-control study, we analyzed tongue P. gingivalis presence and quantification in a large healthy and RA cohort. METHODS: We enrolled 143 RA patients (Male/Female 32/111, mean±SD age 57.5±19.8 years, mean±SD disease duration 155...
July 15, 2018: Clinical and Experimental Immunology
Anqiang Zhang, Wei Gu, Hongxiang Lu, Ling Zeng, Lianyang Zhang, Dingyuan Du, Jiang Hao, Dalin Wen, Xu Wang, Jianxin Jiang
BACKGROUND: Suppressor of cytokine signaling (SOCS) proteins are crucial negative regulators in many signaling pathways and are implicated in the pathogenesis of infectious diseases. The purpose of this study was to uncover possible associations of common polymorphisms within SOCS genes with infectious outcomes after traumatic injury. METHODS: A total of 1087 trauma patients (Chongqing cohort 806 and Yunnan cohort 281) were recruited and followed up for the development of infectious outcomes, such as sepsis and multiple organ dysfunction syndrome (MODS)...
June 19, 2018: Clinical and Experimental Immunology
Yaron Ilan, Kunwar Shailubhai, Arun Sanyal
BACKGROUND: The immune system plays a role in the pathogenesis of NASH underlying hepatocyte injury and fibrosis progression at all disease stages. Oral administration of anti-CD3 monoclonal antibody (mAb) has been shown in pre-clinical studies to be an effective method for systemic immune modulation and alleviates immune-mediated disorders without T-cell depletion. AIM: In the present review, we summarize the concept of the oral administration of humanized anti-CD3 mAb in patients with NASH and discuss the potential of this treatment to address the current requirements of treatments for NASH...
June 19, 2018: Clinical and Experimental Immunology
Xiaokun Gang, Haitao Xu, Lihui Si, Xiujie Zhu, Tong Yu, Zhende Jiang, Yao Wang
OBJECTIVE: The objective of the present study was to evaluate the role of CDKN1A in rheumatoid arthritis (RA). METHODS: Related gene expression data screened from Gene Expression Omnibus (GEO) were processed with network analysis. Protein-protein interaction was analyzed through string database. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to measure mRNA and microRNA expressions. Cell proliferation and cell cycle were tested by MTT assay and flow cytometry respectively...
June 19, 2018: Clinical and Experimental Immunology
Fabrizio De Luca, Yehuda Shoenfeld
The microbiome is represented by microorganisms which live in a symbiotic way with the mammalian. The microorganisms have the ability to influence different physiological aspects such as the immune system, metabolism and behaviour. In the last years, several studies have highlighted the role of the microbiome in the pathogenesis of autoimmune diseases. Notably, in systemic lupus erythematosus an alteration of the intestinal flora (lower Firmicutes/Bacteroidetes ratio) was described. On the other hand, changes to the gut commensal and periodontal disease were proposed as important factors to the pathogenesis of rheumatoid arthritis...
June 19, 2018: Clinical and Experimental Immunology
Marina Dunaeva, Jan Blom, Rogier Thurlings, Ger J M Pruijn
Small non-coding RNAs have emerged as possible biomarkers for various diseases including autoimmune diseases. A number of studies have demonstrated that the expression of specific miRNAs is dysregulated in rheumatoid arthritis (RA). So far all studies on miRNAs in RA patients have been done using either microarray or reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analyses. Compared to RT-qPCR and microarray analyses, next-generation sequencing (NGS) allows the genome-wide analysis of small RNAs and the differentiation between miRNAs that differ by a single nucleotide...
June 12, 2018: Clinical and Experimental Immunology
Alessandra Tammaro, Sandrine Florquin, Mascha Brok, Nike Claessen, Loes M Butter, Gwendoline J D Teske, Onno J de Boer, Thomas Vogl, Jaklien C Leemans, Mark C Dessing
Despite advances in our understanding of the mechanisms underlying progression of chronic kidney disease and the development of fibrosis, only limited efficacious therapies exist. The calcium binding protein S100A8/A9, is a damage-associated molecular pattern which can activate TLR4 or RAGE. Activation of these receptors is involved in the progression of renal fibrosis, however the role of S100A8/A9 herein remains unknown. Therefore, we analyzed S100A8/A9 expression in patients and mice with obstructive nephropathy and subjected wild-type and S100A9 KO mice lacking the heterodimer S100A8/A9 to Unilateral Ureteral Obstruction (UUO)...
May 10, 2018: Clinical and Experimental Immunology
Nicole E James, Evelyn Cantillo, Matthew T Oliver, Rachael B Rowswell-Turner, Jennifer R Ribeiro, Kyu-Kwang Kim, Clinton O Chichester, Paul A DiSilvestro, Richard G Moore, Rakesh K Singh, Naohiro Yano, Ting C Zhao
Ovarian cancers are known to evade immunosurveillance and to orchestrate a suppressive immune microenvironment. Here we examine the role of human epididymis protein 4 (HE4), an ovarian cancer biomarker, in immune evasion. Through modified subtractive hybridization analyses we have characterized the gene targets of HE4 in human peripheral blood mononuclear cells (PBMCs), and established a preliminary mechanism for HE4-mediated immune failure in ovarian tumors. Upon exposure of purified PMBCs to HE4, osteopontin (OPN) and DUSP6 emerged as the most suppressed and upregulated genes respectively...
May 10, 2018: Clinical and Experimental Immunology
Bruce Weder, Mahdi Mozaffari, Luc Biedermann, Céline Mamie, Anja Moncsek, Lichun Wang, Stephen H Clarke, Gerhard Rogler, Bradford L McRae, Candace L Graff, Pedro A Ruiz, Martin Hausmann
INTRODUCTION: In inflammatory bowel disease (IBD), inflammation is sustained by an exaggerated response of lymphocytes. This results from enhanced expression of anti-apoptotic BCL-2 and BCL-XL associated with a diminished turnover. Azathioprine (AZA) directly targets BCL-2 family-mediated apoptosis. We investigated whether the BCL-2 family expression pattern could be used to predict treatment response to AZA and determined whether BCL-2 inhibitor A-1211212 effectively diminishes lymphocytes and ameliorates inflammation in a model of colitis...
May 10, 2018: Clinical and Experimental Immunology
Austin B Bigley, Forrest L Baker, Richard J Simpson
CMV infection is a potentially fatal complication in patients receiving HSCT, but recent evidence indicates that CMV has strong anti-leukemia effects due in part to shifts in the composition of NK-cell subsets. NK-cells are the primary mediators of the anti-leukemia effect of allogeneic HSCT and infusion of allogeneic NK-cells has shown promise as a means of inducing remission and preventing relapse of several different hematologic malignancies. The effectiveness of these treatments is limited, however, when tumors express HLA-E, a ligand for the inhibitory receptor NKG2A which is expressed by the vast majority of post-transplant reconstituted and ex vivo expanded NK-cells...
May 8, 2018: Clinical and Experimental Immunology
Thomas Crowley, Christopher D Buckley, Andrew R Clark
All organisms are constantly exposed to a variety of infectious and injurious stimuli. These induce inflammatory responses tailored to the threat posed. Whilst the innate immune system is the front line of response to each stimulant, it has been traditionally considered to lack memory, acting in a generic fashion until the adaptive immune arm can take over. This outmoded simplification of the roles of innate and acquired arms of the immune system has been challenged by evidence of myeloid cells altering their response to subsequent encounters based on earlier exposure...
May 5, 2018: Clinical and Experimental Immunology
Laura Kraayvanger, Peter Berlit, Philipp Albrecht, Hans-Peter Hartung, Markus Kraemer
INTRODUCTION: Reversible Cerebral Vasoconstriction Syndrome (RCVS) is characterized by an acute onset of severe headache and multifocal segmental vasoconstriction of cerebral arteries resolving within twelve weeks. Diagnostic criteria include normal or near-normal findings in cerebrospinal fluid (CSF) analysis, especially leukocyte levels < 10/mm³. Distinguishing RCVS from primary angiitis of the central nervous system (PACNS) is essential to avoid unnecessary and sometimes unfavorable immunosuppressive treatment...
May 3, 2018: Clinical and Experimental Immunology
Yuanyuan Zhu, Yan Yue, Sidong Xiong
B6/lpr mouse strain is a well-known systemic lupus erythematosus murine model characterized by uncontrolled lymphoproliferation and autoantibody production. However, it displays a delayed and mild development of lupus nephritis (LN), which is not conducive to the research of the pathogenesis and therapeutic strategies of this condition. Our previous study demonstrated that activated lymphocyte-derived DNA (ALD-DNA) could induce high urine protein levels and severe glomerulonephritis (GN) in BALB/c mice. In the present study, we tried to remedy delayed urine protein production and mild GN in B6/lpr mice via ALD-DNA immunization...
April 28, 2018: Clinical and Experimental Immunology
Bonnie J B Lewis, Danila Leontyev, Anton Neschadim, Megan Blacquiere, Donald R Branch
Previously, we reported that interleukin 4 (IL-4), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin 11 (IL-11), but not interleukin 33 (IL-33), are up-regulated in two strains of mice with immune thrombocytopenia (ITP) that are responsive to intravenous immunoglobulin (IVIg) treatment. Previously, IL-4 was ruled out in the mechanism of IVIg; however, other publications have suggested this cytokine as a major player in the mechanism of IVIg action. Thus, we sought to further investigate a role for IL-4 and, in addition, GM-CSF and IL-11 in the mechanism of action of IVIg using a murine model of ITP...
April 28, 2018: Clinical and Experimental Immunology
Asaf Shemer, Shay Kivity, Ora Shovman, Ori Perry, Abdulla Watad, Dana Ben-Ami Shor, Alex Volkov, Iris Barshack, Nicola L Bragazzi, Alexander Krule, Mati Fridkin, Howard Amital, Miri Blank, Yehuda Shoenfeld
BACKGROUND: The role of helminth treatment in autoimmune diseases is constantly growing. Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease with challenging treatment options. Tuftsin phosphorylcholine (TPC) is a novel helminth-based compound that modulates the host immune network. OBJECTIVES: This study was conducted to evaluate the potential value of TPC in ameliorating lupus nephritis in a murine model and specifically to compare the efficacy of TPC to the existing first-line therapy for SLE: corticosteroids (methylprednisolone)...
April 26, 2018: Clinical and Experimental Immunology
Agnieszka Jabłońska, Mirosława Studzińska, Patrycja Suski, Jarosław Kalinka, Edyta Paradowska
The innate immune response in the placenta depends on the ability of maternal immune cells and fetal trophoblast cells to detect and eliminate invading pathogens through germline-encoded pattern recognition receptors (PRRs). In the present study, we analyzed the transcripts and protein expression of IFI16, MDA5, RIG-I, and TLR3 in third-trimester human placentas and investigated cytokine profiles generated during herpes simplex type 1 (HSV-1) infection. Decidual and chorionic villous biopsies (38-42 week of gestation) were obtained from healthy women immediately after a cesarean section...
April 24, 2018: Clinical and Experimental Immunology
G S Stødle, G B Silva, L H Tangerås, L M Gierman, I Nervik, U E Dahlberg, C Sun, M H Aune, L C V Thomsen, L Bjørge, A-C Iversen
Pre-eclampsia is associated with increased levels of cholesterol and uric acid and an inflamed placenta expressing danger-sensing pattern recognition receptors (PRRs). Crystalline cholesterol and uric acid activate the PRR Nod-like receptor protein (NLRP)3 inflammasome to release interleukin (IL)-1β and result in vigorous inflammation. We aimed to characterize crystal-induced NLRP3 activation in placental inflammation and examine its role in pre-eclampsia. We confirmed that serum total cholesterol and uric acid were elevated in pre-eclamptic compared to healthy pregnancies and correlated positively to high sensitivity C-reactive protein (hsCRP) and the pre-eclampsia marker soluble fms-like tyrosine kinase-1 (sFlt-1)...
April 23, 2018: Clinical and Experimental Immunology
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