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Clinical and Experimental Immunology

J R Fergusson, J E Ussher, A Kurioka, P Klenerman, L J Walker
High expression of the ATP-binding cassette-multi-drug efflux protein 1 (MDR1) is a striking feature of mucosal-associated invariant T (MAIT) cells, a prominent human innate-like T cell subset. We demonstrate significantly higher MDR1 expression by CD8 + CD161 ++ Vα7.2 + MAIT cells than the phenotypically and functionally related CD8 + CD161 ++ Vα7.2-subset and show MDR1 expression to be similarly high throughout MAIT CD4 + , CD8 + , double-negative (DN) and double-positive (DP) cell subsets. We demonstrate the MAIT cell-predominant CD8+ CD161++ subset to uniquely and efficiently efflux the cytotoxic anthracycline daunorubicin, retain function on daunorubicin exposure and demonstrate MDR1-dependent protection from daunorubicin-induced apoptosis...
September 19, 2018: Clinical and Experimental Immunology
Jinpiao Lin, Yujue He, Binglong Wang, Zhen Xun, Shanjian Chen, Zhiyong Zeng, Qishui Ou
OBJECTIVES: Our previous study has revealed that YY1 played an important part in promoting IL-6 production in rheumatoid arthritis (RA). However, whether YY1 has any role in regulation of IL-8 in RA remains unclear. MATERIALS AND METHODS: YY1 and IL-8 expression in RA patients were analyzed by real-time PCR. Ingenuity pathway analysis (IPA) was used to analyzed signaling pathway involved in YY1-induced IL-8 production. The expression of YY1 and proteins involved in pathway were detected by western blot and ELISA...
September 19, 2018: Clinical and Experimental Immunology
M-N Theodoraki, T K Hoffmann, E K Jackson, T L Whiteside
Exosomes in plasma of head and neck squamous cell carcinoma (HNSCC) patients comprise subsets of vesicles derived from various cells. Recently, we separated CD3(+) from CD3(-) exosomes by immune capture. CD3(-) exosomes were largely tumour-derived (CD44v3+ ). Both subsets carried immunosuppressive proteins and inhibited functions of human immune cells. The role of these subsets in immune cell reprogramming by the tumour was investigated by focusing on the adenosine pathway components. Spontaneous adenosine production by CD3(+) or CD3(-) exosomes was measured by mass spectrometry, as was the production of adenosine by CD4+ CD39+ regulatory T cells (Treg ) co-incubated with these exosomes...
September 19, 2018: Clinical and Experimental Immunology
Maryiam Zaman, Aarnoud Huissoon, Matthew Buckland, Smita Patel, Hana Alachkar, J David Edgar, Moira Thomas, Gururaj Arumugakani, Helen Baxendale, Siobhan Burns, Anthony P Williams, Stephen Jolles, Richard Herriot, Ravishankar B Sargur, Peter D Arkwright
Good's syndrome (thymoma and hypogammaglobulinemia) is a rare secondary immunodeficiency disease, previously reported in the published literature as mainly individual cases or small case series. We use the national UK-Primary Immune Deficiency (UKPID) registry to identify a large cohort of patients in the UK with this PID to review its clinical course, natural history and prognosis. Clinical information, laboratory data, treatment and outcome were collated and analysed. Seventy-eight patients with a median age of 64 years, 59% of whom were females were reviewed...
September 14, 2018: Clinical and Experimental Immunology
Petra Lüthje, Simona Walker, Witchuda Kamolvit, Soumitra Mohanty, Katrin Pütsep, Annelie Brauner
Antimicrobial resistance increases among bacterial pathogens and new therapeutic avenues needs to be explored. Boosting innate immune mechanisms could be one attractive alternative in the defense against infectious diseases. The cholesterol-lowering drugs, statins, have been demonstrated to also affect the immune system. Here we investigate the effect of statins on the expression of the human cathelicidin antimicrobial peptide LL-37/hCAP-18 (encoded by the CAMP gene) and explore the underlying mechanisms in four epithelial cell lines of different origin...
September 14, 2018: Clinical and Experimental Immunology
Qing Luo, Lu Zhang, Xue Li, Biqi Fu, Zhen Deng, Cheng Qing, Rigu Su, Jianqing Xu, Yang Guo, Zikun Huang, Junming Li
Circular RNAs (circRNAs) are a new class of RNAs can be used as biomarkers in clinical blood samples. However, little is known about circRNAs' diagnostic values for rheumatoid arthritis (RA). In this study, the hsa_circ_0054189, hsa_circ_0008675, hsa_circ_0082689, hsa_circ_0082688, hsa_circ_0010932, hsa_circ_0002473 and hsa_circ_0044235 in peripheral blood were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Hsa_circ_0044235, only one abnormal expression circRNAs in peripheral blood was selected as a targeted circRNA to explore the diagnostic value for RA...
September 14, 2018: Clinical and Experimental Immunology
M Frodlund, A Vikerfors, G Grosso, T Skogh, J Wetterö, K Elvin, I Gunnarsson, A Kastbom, Ö Dahlström, J Rönnelid, E Svenungsson, C Sjöwall
Immunoglobulin (Ig) G- and IgM-class anti-cardiolipin antibodies (aCL) and lupus anti-coagulant (LA) are included in the 1997 update of the American College of Rheumatology (ACR-97) systemic lupus erythematosus (SLE) criteria. Despite limited evidence, IgA-aCL and IgA anti-β2 -glycoprotein-I (anti-β2 GPI) were included in the 2012 Systemic Lupus International Collaborating Clinics criteria. The present study aimed to evaluate IgG-/IgA-/IgM-aCL and anti-β2 GPI occurrence in relation to disease phenotype, smoking habits, pharmacotherapy, anti-phospholipid syndrome (APS) and organ damage among 526 Swedish SLE patients meeting ACR-97...
September 12, 2018: Clinical and Experimental Immunology
Catalina Álvarez-Larrotta, Olga María Agudelo, Yesica Duque, Kenneth Gavina, Stephanie K Yanow, Amanda Maestre, Jaime Carmona-Fonseca, Eliana Arango
Submicroscopic Plasmodium infections in pregnancy are common in endemic areas and it is important to understand the impact of these low level infections. Asymptomatic, chronic infections are advantageous for parasite persistence, particularly in areas where the optimal eco-epidemiologic conditions for parasite transmission fluctuate. In chronic infections, the persistence of the antigenic stimulus changes the expression of immune mediators and promotes constant immune regulation, including increases in regulatory T cell populations...
September 8, 2018: Clinical and Experimental Immunology
Yoshio Osada, Yukari Horie, Susumu Nakae, Katsuko Sudo, Tamotsu Kanazawa
To investigate possible roles of Th2 cytokines in the anti-arthritic effects of a blood fluke, Schistosoma mansoni (Sm), for mouse collagen-induced arthritis (CIA), wild-type (WT), STAT6KO and IL-10KO mice were infected with Sm. Three weeks after infection, the mice were immunized with bovine type II collagen (IIC). Arthritis severity was monitored by scoring, measurement of paw thickness and the presence of ankylosis. Serum anti-IIC IgG levels, splenic cytokine production, and cytokine gene expression in the popliteal lymph nodes (PLNs) were measured and compared among WT and gene-KO mice...
September 8, 2018: Clinical and Experimental Immunology
Susanna Brauner, Margarita Ivanchenko, Gudny Ella Thorlacius, Aurelie Ambrosi, Marie Wahren-Herlenius
Systemic rheumatic diseases are characterised by abnormal B cell activation with autoantibody production and hypergammaglobulinemia. Ro52/SSA, also denoted TRIM21, is a major autoantigen in Sjögren's syndrome and systemic lupus erythematosus. Interestingly, TRIM21-deficient mice develop systemic autoimmunity with B cell-driven manifestations such as autoantibodies, hypergammaglobulinemia and glomerulonephritis following tissue injury. The mechanisms by which TRIM21-deficiency leads to enhanced B cell activation and antibody production are however not well understood, and to further elucidate the role of TRIM21 in systemic autoimmunity, we investigated the B cell phenotype and antibody responses of Trim21-/- mice following immunisation with thymus-dependent (TD) and thymus-independent (TI) antigens...
September 3, 2018: Clinical and Experimental Immunology
T Nagano, M Katase, K Tsumura
Soyasaponins (SSs) are abundant in soybeans and display inhibitory activity against contact hypersensitivity (CHS), which is often used as a mouse model for allergic contact dermatitis (ACD); however, their therapeutic mechanisms remain unknown. Here, we attempted to clarify the role of gut microbiota in the inhibition of CHS by dietary soyasaponins. For antibiotic treatment, mice were administered a mixture of ciprofloxacin and metronidazole or vancomycin. These antibiotics and SSs were given to mice via drinking water 3 weeks prior to CHS induction with 2,4-dinitrofluorobenzene, and the mice were analysed for ear swelling, tissue oedema, infiltration of Gr-1-positive immune cells, the composition of faecal microbiota, and regulatory T (Treg ) cells...
September 3, 2018: Clinical and Experimental Immunology
Joud Hajjar, Carleigh Kutac, Nicholas L Rider, Filiz O Seeborg, Christopher Scalchunes, Jordan S Orange
INTRODUCTION: Patients with Common Variable Immunodeficiency (CVID) have increased fatigue compared with the general population. Fatigue is associated with lower quality of life (QoL), which is associated with higher mortality in CVID. OBJECTIVE: This study aimed to determine the prevalence of self-reported fatigue for patients with CVID and to identify its possible drivers and burden on QoL. METHODS: We analyzed data the 2013 Immune Deficiency Foundation (IDF) treatment survey...
August 31, 2018: Clinical and Experimental Immunology
Alexander Hellesen, Eirik Bratland
Autoimmune Addison's disease (AAD), or primary adrenocortical insufficiency, is a classical organ-specific autoimmune disease with160 years of history. AAD is remarkably homogenous with one major dominant self-antigen, the cytochrome P450 21-hydroxylase enzyme, which is targeted by both autoantibodies and autoreactive T cells. Like most autoimmune diseases, AAD is thought to be caused by an unfortunate combination of genetic and environmental factors. While the number of genetic associations with AAD is increasing, almost nothing is known about environmental factors...
August 24, 2018: Clinical and Experimental Immunology
Zhaoyang Li, Susan Richards, Howard K Surks, Alan Jacobs, Michael A Panzara
Alemtuzumab, a humanized anti-CD52 monoclonal antibody, is approved for treatment of relapsing MS. In the Phase 2/3 trials, patients received 12 or 24 mg/day of alemtuzumab in two treatment courses (5 days for Course 1 and 3 days for Course 2), 12 months apart. Serum concentrations of alemtuzumab peaked on the last day of dosing in each course and mostly fell below the limit of quantitation by Day 30. Alemtuzumab rapidly depleted circulating T and B lymphocytes, with the lowest observed values occurring within days...
August 24, 2018: Clinical and Experimental Immunology
Alf Kastbom, Karin Roos Ljungberg, Michael Ziegelasch, Jonas Wetterö, Thomas Skogh, Klara Martinsson
Rheumatoid arthritis (RA) is a chronic inflammatory disease where serum analysis of anti-citrullinated peptide/protein antibodies (ACPA) is an important diagnostic/prognostic tool. Levels and changes of ACPA in RA patients have previously been studied in relation to disease course and therapy response, but less is known regarding ACPA isotype changes in early RA. Hence, recent-onset RA patients (n=231) were subjected to a 3-year clinical and radiological follow-up. Serum samples were serially collected and ACPA isotypes were analysed using the 2nd generation CCP as capture antigen...
August 23, 2018: Clinical and Experimental Immunology
Wan-Chien Cheng, Fahd Saleh, Belkais Abuaisha Karim, Francis J Hughes, Leonie S Taams
Periodontitis is a chronic inflammatory disease caused by the colonisation of teeth by the bacterial plaque biofilm and the resultant host immune responses in adjacent periodontal tissues. Disease severity can vary dramatically between patients with periodontitis, with some subjects displaying inflammation without bony destruction (gingivitis), whilst others experience chronic progressive or rapidly aggressive gingival connective tissue damage and bone loss. To determine whether peripheral immune dysregulation is associated with periodontitis, we performed extensive analysis of immune cell subsets in peripheral blood from patients with chronic or aggressive periodontitis vs...
August 18, 2018: Clinical and Experimental Immunology
Urs Christen, Edith Hintermann
Autoimmune hepatitis (AIH) is a severe form of hepatitis resulting in the autoimmune-mediated destruction of the liver parenchyma. Whereas many of the immunopathogenic events have been elucidated and some of the drivers of the disease have been identified, not much is known about the etiology of the disease. There are certain risk factors, such as particular HLA haplotypes, that enhance the susceptibility for AIH or influence the severity of the disease. However, as for many other autoimmune diseases, the mere presence of such risk factors does not warrant the occurrence of the disease...
August 16, 2018: Clinical and Experimental Immunology
Jiawen Cui, Yabin Zhou, Huimin Hu, Lanqing Zhao, Zhongdong Du, Hongwu Du
Kawasaki disease (KD) is an immune-mediated vasculitis with symptoms mimic febrile illness, the immune origin has been suggested but never proved. Firstly, cell chip technology was used to screen immune targets cells, with the indirect immunofluorescence assay we found that HeLa cell chip could be recognized by KD patient serum samples. Then the target cell proteome was extracted as antigens, and antigen recognition reaction was performed using the patients' serum as antibodies, the detected target protein was detected and identified as Phosphoglycerate Kinase 1 (PGK1)...
August 16, 2018: Clinical and Experimental Immunology
Jingyun Xu, Lijia Wu, Pengcheng Yu, Mingxu Liu, Yixin Lu
Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease (CD), is a chronic autoimmune disease. Parasitic infections and their products have been shown protective effects on autoimmune diseases, including IBD. In this experiment, 96 male BALB/c mice aged 6-8 weeks were randomly divided into two large groups: prevention group and therapy group. The changes on the various indicators of colitis were detected to demonstrate that T. spiralis serine protease inhibitors can relieve the inflammatory severity of TNBS-induced colitis and to explore possible immunological mechanisms...
August 13, 2018: Clinical and Experimental Immunology
Yufan Chen, Xinqiong Wang, Yi Yu, Yuan Xiao, Jiebin Huang, Zhanyong Yao, Xuehua Chen, Tong Zhou, Pu Li, Chundi Xu
Emerging evidence has linked the exosomes to many immunological disorders, including infectious diseases. However, knowledge regarding the role of exosomes in Helicobacter pylori infection is limited. Here, we show that serum exosomes from chronic gastritis patients with H. pylori infection (Hp exosomes) stimulate the expression of the soluble IL-6 receptor (sIL-6R), which is involved in IL-6 trans-signaling in gastric epithelial cells. Interestingly, sIL-6R upregulates the expression of the pro-inflammatory cytokine IL-1α, and the neutralization of sIL-6R suppresses IL-1α secretion...
August 13, 2018: Clinical and Experimental Immunology
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