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Clinical and Experimental Immunology

Michael Terence Boswell, Sarah Rowland-Jones
HIV-2 is thought to have entered the human population in the 1930s through cross-species transmission of SIV from sooty mangabeys in West Africa. Unlike HIV-1, HIV-2 has not led to a global pandemic and recent data suggest that HIV-2 prevalence is declining in some West African states where it was formerly endemic. Although many early isolates of HIV-2 were derived from patients presenting with AIDS-defining illnesses, it was noted that a much larger proportion of HIV-2-infected subjects behaved as long-term non-progressors (LTNP) than their HIV-1-infected counterparts...
February 17, 2019: Clinical and Experimental Immunology
X Teng, W Li, C Cornaby, L Morel
Immune metabolism is a rapidly moving field. While most of the research has been conducted to define the metabolism of healthy immune cells in the mouse, it is recognized that the overactive immune system that drives autoimmune diseases presents metabolic abnormalities that provide therapeutic opportunities, as well as a means to better understand the fundamental mechanisms of autoimmune activation. Here, we review recent publications that have reported how the major metabolic pathways are affected in autoimmune diseases, with a focus on rheumatic diseases...
February 15, 2019: Clinical and Experimental Immunology
Erik Nutma, Hugh Willison, Martino Gianvito, Sandra Amor
Neuroimmunology as a separate discipline has its roots in the fields of neurology, neuroscience and immunology. Early studies of the brain by Golgi and Cajal, the detailed clinical and neuropathology studies of Charcot, and Thompson's seminal paper on graft acceptance in the central nervous system kindled a now rapidly expanding research area with the aim of understanding pathological mechanisms of inflammatory components of neurological disorders. Whilst neuroimmunologists originally focussed on classical neuroinflammatory disorders such as multiple sclerosis and infections, there is strong evidence to suggest that the immune response contributes to genetic white matter disorders, epilepsy, neurodegenerative diseases, neuropsychiatric disorders, peripheral nervous system and neuro-oncological conditions, as well as ageing...
February 15, 2019: Clinical and Experimental Immunology
Sinuhe Hahn, Paul Hasler, Lenka Vokalova, Shane V van Breda, Olav Lapaire, Gabor Nandor Than, Irene Hoesli, Simona W Rossi
Neutrophils are often exclusively considered as first line innate immune defence, able to rapidly kill or trap pathogens and causing in case of over activation tissue damage. In the female reproductive tract, however, the presence and activity of neutrophils seem to be tightly regulated. Major players in orchestrating this regulation are cyclical steroid sex hormones present during the menstrual cycle and pregnancy. This review describes the role of sex hormones in regulating directly or indirectly the functionality of neutrophils, the role of neutrophils during fertilisation and pregnancy and in controlling viral, fungal and bacterial infection...
February 15, 2019: Clinical and Experimental Immunology
Calum D Moulton, Polychronis Pavlidis, Christine Norton, Sam Norton, Carmine Pariante, Bu Hayee, Nick Powell
Depressive symptoms are reported by more than 20% of people with inflammatory bowel disease (IBD), whilst sleep difficulties and fatigue are even more common. Comorbid depressive symptoms predict a poor IBD course, including increased risk of relapse and surgery, which is inconsistently improved by psychological treatments. Rather than being distinct systems, there is compelling evidence for bidirectional communication between gut and brain, driven by neural, metabolic, endocrine and inflammatory mediators...
February 14, 2019: Clinical and Experimental Immunology
Thomas F Rice, Dimitri A Diavatopoulos, Gaby P Smits, Pieter van Gageldonk, Guy Berbers, Fiona van der Klis, George Vamvakas, Beverly Donaldson, Marielle Bouqueau, Beth Holder, Beate Kampmann
The maternal Tdap (tetanus, diphtheria and acellular pertussis) vaccination program in the UK has successfully reduced cases of pertussis in young infants. In addition to prevention of pertussis cases, it is also important to investigate persistence of maternal antibody during infancy and possible interference of maternal antibodies with infant responses to vaccines. We recruited mother-infant pairs from vaccinated and unvaccinated pregnancies and measured concentrations of IgG against pertussis toxin (PTx), filamentous hemagglutinin (FHA), pertactin (Prn), diphtheria toxin (DTx), tetanus toxoid (TTx) Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae in mothers and infants at birth, and in infants at 7 weeks and at 5 months...
February 13, 2019: Clinical and Experimental Immunology
Jacopo Meldolesi
Two types of extracellular vesicles (EVs), exosomes and ectosomes, are generated and released by all cells, including immune cells. The two EVs appear different in many properties: size, mechanism and site of assembly, composition of their membranes and luminal cargoes, sites and processes of release. In functional terms, however, these differences are minor. Moreover, their binding to and effects on target cells appear similar thus the two types are considered distinct only in a few cases, otherwise they are presented together as EVs...
February 13, 2019: Clinical and Experimental Immunology
M Pérez-Ferro, F I Romero-Bueno, C Serrano Del Castillo, I Mahillo, A Alvear, R Largo, G Herrero-Beaumont, O Sánchez-Pernaute
The MHC class I-related chain A (MICA) is induced upon stress and labels malfunctioning cells for their recognition by cytotoxic lymphocytes. Alterations in this recognition and also abnormal natural killer (NK) functions have been found in SLE. MICA can be shed from cells, subsequently acting as a soluble decoy receptor (sMICA). Our purpose was to study circulating sMICA levels in relationship with the activation of innate pathways in PBMC in a cohort of lupus patients. NK cells were characterized by flow cytometry...
February 8, 2019: Clinical and Experimental Immunology
Kathrin Arndts, Tayseer Elamin Mohamed Elfaki, Nils Jelden, Manuel Ritter, Anna Wiszniewsky, Gnatoulma Katawa, Ibtisam A Goreish, Misk El Yemen A Atti El Mekki, Michael J Doenhoff, Achim Hoerauf, Laura E Layland
Infections with Schistosoma mansoni remain a major health problem in the Sudan where endemic communities, such as those in Kassala and Khartoum states, continue to face severe social-economic difficulties. Our previous immunoepidemiological findings revealed different immune (cytokine and S. mansoni egg (SEA) antibody) profiles in individuals with active infections (eggs in stool n=110), individuals positive for S. mansoni via PCR using sera (SmPCR+ n=63) and those uninfected (Sm uninf). Since antibody responses to eggs and worms are known to change during infection we have expanded the profiling further by determining levels of adult worm (SWA) antibodies and nine chemokines in the serum of each individual in the three different cohorts...
February 6, 2019: Clinical and Experimental Immunology
Katsuhiro Oi, Tadahiro Tokunaga, Tatsuomi Kuranobu, Kazutoshi Yukawa, Hiroki Kohno, Yusuke Yoshida, Sho Mokuda Shintaro Hirata, Eiji Sugiyama
CTLA-4-Ig exerts anti-rheumatic action via negative regulation of the co-stimulation process between antigen-presenting cells and T cells. CTLA-4-Ig also binds to CD80/CD86 on monocytes of osteoclast precursors. However, little is known about the effect of CTLA-4-Ig on osteoclastogenesis in rheumatoid arthritis (RA). We evaluated here the effects of CTLA-4-Ig on osteoclast generation from human blood monocytes (PBM) and rheumatoid synovial fluid monocytes (RSFM). Highly purified monocytes were cultured with RANKL and M-CSF in the presence of CTLA-4-Ig...
February 6, 2019: Clinical and Experimental Immunology
Claire Bethune, William Egner, Tomaz Garcez, Aarnoud Huissoon, Stephen Jolles, Yousuf Karim, Rashmi Jain, Sinisa Savic, Kate Kelley, Dorothea Grosse-Kreul, Sofia Grigoriadou
Common variable immunodeficiency (CVID) represents a heterogeneous group of rare disorders. There is considerable morbidity and mortality as a result of non-infectious complications and this presents clinicians with management challenges. Clinical guidelines to support the management of CVID are urgently required. The UK Primary Immunodeficiency Network and the British Society for Immunology funded a joint project, to address this. A modified Delphi Survey was conducted for the assessment, diagnosis and treatment of the non-infectious blood, respiratory, gut and liver complications of CVID...
February 6, 2019: Clinical and Experimental Immunology
B Feiner, K A Chase, J K Melbourne, C Rosen, R P Sharma
Epigenetic effects of anti-psychotic medications are poorly understood. We have appropriated a model whereby heterochromatin is established through 24- or 48-h lipopolysaccharide (LPS) treatment, and tested the epigenetic effects of risperidone along the adenylyl cyclase/protein kinase A (AC/PKA) pathway in human liposarcoma cells that express the LPS-sensitive Toll-like receptor (TLR)-4. Human SW872 cells were cultured with LPS and mRNA expression levels and epigenetic modifications of dimethylated lysine 9 of histone 2 (H3K9me2), geterochromatin protein 1γ (HP1γ) and phospho-H3S10 at promoters of interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL1β were measured...
February 3, 2019: Clinical and Experimental Immunology
Cecilia Hagert, Riikka Siitonen, Xiang-Guo Li, Heidi Liljenbäck, Anne Roivainen, Rikard Holmdahl
Psoriasis (Ps), psoriatic arthritis (PsA) and rheumatoid arthritis (RA) are common diseases dependent on environmental factors that activate the immune system in unknown ways. Mannan is a group of polysaccharides common in the environment; they are potentially pathogenic because at least some of them induce Ps-, PsA- and RA-like inflammation in mice. Here, we used positron emission tomography/computed tomography to examine in vivo transport and spread of mannan labelled with 18 F. The results showed that mannan was transported to joints (knee) and bone marrow (tibia) of mice within six hours after intraperitoneal injection...
February 3, 2019: Clinical and Experimental Immunology
Sebastiaan Heidt, Manon Vergunst, Jacqueline D H Anholts, Godelieve M J S Swings, Els M J Gielis, Koen E Groeneweg, Myrèse J Witkamp, Johan W de Fijter, Marlies E J Reinders, Dave L Roelen, Michael Eikmans, Frans H J Claas
B cells have various functions besides being plasma cell precursors. We determined the presence of intragraft B cells at time of acute rejection (AR) and looked for correlates of B cell involvement in peripheral blood. Renal biopsies at time of AR or stable graft function were analyzed for the presence of B cells and B cell-related gene expression, as well as C4d staining. Peripheral blood B cell subset distribution was analyzed at various time-points in patients with AR and controls, alongside serum HLA antibodies...
February 3, 2019: Clinical and Experimental Immunology
Michael R Holt, John J Miles, Warrick J Inder, Rachel Thomson
Lung disease due to nontuberculous mycobacteria (NTM) occurs with disproportionate frequency in postmenopausal women with a unique phenotype and without clinically apparent predisposing factors. Dubbed "Lady Windermere Syndrome", the phenotype includes low body mass index (BMI), tall stature, and higher than normal prevalence of scoliosis, pectus excavatum and mitral valve prolapse. Although the pathomechanism for susceptibility to NTM lung disease in these patients remains uncertain, it is likely to be multifactorial...
January 29, 2019: Clinical and Experimental Immunology
Xinyi Pei, Xueying Fan, Hao Zhang, Hao Duan, Chao Xu, Bingyu Xie, Linghang Wang, Xingwang Li, Yihong Peng, Tao Shen
A minority of hand, foot, and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) results in severe neural complications. However, whether monocyte-mediated immunity is involved in the disease progression of HFMD remains unknown. 120 mild and 103 severe HFMD patients were recruited and ELISA, flow cytometry and transwell culture were performed in the study. Peripheral monocyte counts were lower in both absolute counts and frequencies in severe cases compared to mild cases. After screening 10 monocyte-related cytokines by ELISA, only monocyte chemoattractant protein-1 (MCP-1) was found at higher levels in sera of mild cases compared to those with severe symptoms...
January 29, 2019: Clinical and Experimental Immunology
T Ris, A Teixeira-Carvalho, R Matos Pinto Coelho, C Brandao-de-Resende, M Souza Gomes, L Rodrigues Amaral, P H Oliveira Murta Pinto, L J Souza Santos, J Teixeira Salles, Jolien Roos-Hesselink, N Verkaik, T Cristina Abreu Ferrari, M C Pereira Nunes
Infective endocarditis (IE) is the cardiac disease with the highest rates of mortality. New biomarkers that are able to identify patients at risk for death are required to improve patient management and outcome. This study aims to investigate if cytokines, chemokines and growth factors measured at IE diagnosis can predict mortality. Patients with definite IE, according to the Duke's modified criteria, were included. Using high-performance Luminex assay, 27 different cytokines, chemokines and growth factors were analyzed...
January 29, 2019: Clinical and Experimental Immunology
Salman M Toor, Varun Sasidharan Nair, Gerald Pfister, Eyad Elkord
Tumor immune evasion involves expansion of avidly proliferating, immunosuppressive cells and inhibition of effector T cell proliferation. Immune checkpoints (IC) block the activation pathways of tumor-reactive T cells. IC pathways are often exploited by tumor cells to evade immune destruction, and blocking these pathways through IC inhibitors (ICI) has shown promising results in multiple malignancies. In this study, we investigated the effects of an ICI, pembrolizumab, on various T cell subsets in vitro. We compared the suppressive activity of CD4+ CD25+ regulatory T cells (conventional Treg) with T cells expressing T cell immunoglobulin-3+ (TIM-3+ ) and LAP+ T cells...
January 28, 2019: Clinical and Experimental Immunology
K Hudspeth, S Wang, J Wang, S Rahman, M A Smith, K A Casey, Z Manna, M Sanjuan, R Kolbeck, S Hasni, R Ettinger, R M Siegel
Systemic Lupus Erythematosus (SLE) is a complex autoimmune disorder whose pathology involves multiple immune cell types, including B and T lymphocytes as well as myeloid cells. While it is clear that autoantibody producing B cells as well as CD4+ T cell help are key contributors to disease, little is known regarding the role of innate lymphoid cells such as Natural Killer (NK) cells in the pathogenesis of SLE. We have characterized the phenotype of NK cells by multicolor flow cytometry in a large cohort of SLE patients...
January 28, 2019: Clinical and Experimental Immunology
Vanessa Beatriz Freitas Alves, Beatriz Coutinho de Sousa, Monique Thaís Costa Fonseca, Haline Ogata, Carolina Caliári-Oliveira, Juliana Navarro Ueda Yaochite, Virmondes Rodrigues Júnior, Javier Emílio Lazo Chica, João Santana da Silva, Kelen Cristina Ribeiro Malmegrim, Larissa Pernomian, Cristina Ribeiro Cardoso
Current therapies for Inflammatory Bowel Diseases (IBD) are aimed at controlling the exacerbated response in the gut, but no treatment is fully effective for several refractory patients. Mesenchymal stromal cells (MSC) are multipotent cells with regulatory immunosuppressive activity that may control inflammatory diseases. Then, here we investigated the short and specially the long-term protective effects of MSC on experimental colitis. We showed that MSC elicited protection to acute intestinal inflammation with gain of weight, improvement in the clinical disease score and expressive reduction in the mortality rate of treated mice...
January 21, 2019: Clinical and Experimental Immunology
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