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Clinical and Experimental Immunology

Max Brown, Steven O'Reilly
Systemic sclerosis (SSc) is an idiopathic systemic autoimmune disease. It is characterised by a triad of hallmarks: immune dysfunction, fibrosis and vasculopathy. Immune dysfunction in SSc is characterised by the activation and recruitment of immune cells and the production of autoantibodies and cytokines. How immune abnormalities link the fibrosis and vasculopathy in SSc is poorly understood. A plethora of immune cell types are implicated in the immunopathogenesis of SSc including: T cells, B cells, dendritic cells, mast cells, and macrophages...
November 14, 2018: Clinical and Experimental Immunology
Alla Splichalova, Vera Jenistova, Zdislava Splichalova, Igor Splichal
A balanced microbiota of the gastrointestinal tract (GIT) is a prerequisite for a healthy host. The GIT microbiota in preterm infants is determined by the method of delivery and nutrition. Probiotics can improve the GIT microbiota balance and suitable animal models are required to verify their harmlessness. Preterm gnotobiotic piglets were colonized with Lactobacillus rhamnosus GG (LGG) to evaluate its safety and possible protective action against infection with an enteric pathogen, Salmonella Typhimurium (ST)...
November 13, 2018: Clinical and Experimental Immunology
Z Zhong, M Haltalli, B Holder, T Rice, B Donaldson, M O'Driscoll, K Le-Doare, B Kampmann, J S Tregoning
Pregnant women and infants are at an increased risk of severe disease after influenza infection. Maternal immunisation is a potent tool to protect both of these at-risk groups. Whilst the primary aim of maternal influenza vaccination is to protect the mother, a secondary benefit is the transfer of protective antibodies to the infant. A recent study using the tetanus, diphtheria and acellular pertussis (Tdap) vaccine indicated that children born to mothers immunised in the second trimester of pregnancy had the highest antibody titres compared to children immunised in the third trimester...
November 13, 2018: Clinical and Experimental Immunology
Martijn H J van den Bosch
Osteoarthritis (OA) is the most common joint disease that strongly reduces the quality of life in patients. Yet, no disease-modifying therapy is available. For a long time, OA was considered a non-inflammatory disease that was the result of 'wear and tear' and abnormal mechanics and therefore many considered the term osteoarthritis a misnomer. However, over the last decades, the notion arose that inflammation is not only present in the majority of OA patients, but rather actively involved in the progression of the disease...
November 13, 2018: Clinical and Experimental Immunology
Akihiro Doi, Shigeyuki Kano, Mai Asano, Yuko Takahashi, Takahiro Mimori, Akio Mimori, Hiroshi Kaneko
A genetic variant of the killer immunoglobulin-like receptor 3DL1 (KIR3DL1) has been found in patients with systemic lupus erythematosus (SLE). Herein, we investigated the presence of autoantibodies to KIR3DL1 in a cohort of patients with SLE. We tested sera from 28 patients with SLE, 11 patients with rheumatoid arthritis (RA), and 17 healthy control subjects for anti-KIR3DL1 activity by an enzyme-linked immunosorbent assay (ELISA) using recombinant KIR3DL1-EGFP and EGFP proteins. Anti-KIR3DL1 antibodies were detected in 22 (79%) out of the 28 patients with SLE, whereas they were present only in three (27%) out of the 11 patients with RA examined...
November 13, 2018: Clinical and Experimental Immunology
Franziska Wiese, Katharina Reinhardt-Heller, Mareike Volz, Christian Gille, Natascha Köstlin, Heiko Billing, Rupert Handgretinger, Ursula Holzer
Extracorporeal photopheresis (ECP) is a widely used immunomodulatory therapy for the treatment of various T-cell mediated disorders like cutaneous T-cell lymphoma (CTCL), graft-versus-host disease (GvHD), or systemic sclerosis. Although clinical benefits of ECP are already well described, the underlying mechanism of action of ECP is not fully understood yet. Especially knowledge on the fate of CD14+ monocytes in the context of ECP is limited and controversial. Here, we investigated the immunoregulatory function of ECP treated monocytes on T-cells in an in vitro ECP model...
November 8, 2018: Clinical and Experimental Immunology
Mingen Lyu, Yang Li, Yating Hao, Cuicui Lyu, Yueting Huang, Boyang Sun, Huiyuan Li, Feng Xue, Xiaofan Liu, Renchi Yang
Current researches have determined the significance of CCR6 expression as either a marker of T helper cells(Th) or as an effector and regulator of T cell function. However, the roles of CCR6 in the pathogenesis of immune thrombocytopenia (ITP) are unclear. In this study, we aimed to investigate the phenotype and functional characteristics of circulating CCR6+ T cells in blood from chronic ITP patients and healthy controls. We found that the frequency of CCR6+ CD4+ cells was higher in ITP patients than in healthy controls...
November 7, 2018: Clinical and Experimental Immunology
A Berglund, L Cleemann, B E Oftedal, K Holm, E S Husebye, C H Gravholt
Turner syndrome (TS) is associated with an increased frequency of autoimmunity. Frequently observed autoimmune diseases in TS are also seen in the autoimmune polyendocrine syndrome type I (APS I), of which Addison disease is a key component. An overlapping antibody profile between TS and APS I could be considered. The aim of this work was to study women with TS regarding 21-hydroxylase (21-OH) antibodies and interferon omega (IFN-ω) antibodies, a highly specific marker for APS I, to determine if there are immunological overlaps between TS and APS I...
October 29, 2018: Clinical and Experimental Immunology
S Virachith, M Saito, Y Watanabe, K Inoue, O Hoshi, T Kubota
Autoantibodies characteristic for antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) are anti-β2 -glycoprotein I (β2 GPI) antibodies and anti-DNA antibodies, respectively, and nearly half of APS cases occur in SLE. Anti-β2 GPI antibodies are recognized to play a pivotal role in inducing a prothrombotic state, but the precise mechanism has not been fully elucidated. In a widely-accepted view, binding of anti-β2 GPI antibodies to cell surface β2 GPI in monocytes and endothelial cells triggers the TLR4-MyD88 signaling pathway which leads to activation of p38 MAPK, MEK-1/ERK, and/or NF-κB, and expression of tissue factor (TF)...
October 28, 2018: Clinical and Experimental Immunology
Nils Rosshirt, Sébastien Hagmann, Elena Tripel, Tobias Gotterbarm, Johannes Kirsch, Felix Zeifang, Hanns-Martin Lorenz, Theresa Tretter, Babak Moradi
Thorough understanding of the complex pathophysiology of osteoarthritis (OA) is necessary in order to open new avenues for treatment. The aim of this study was to characterize the CD4+ T cell population and evaluate their activation and polarization status in OA joints. 55 patients with end-stage knee OA (Kellgren-Lawrence grade III-IV) who underwent surgery for total knee arthroplasty (TKA) were enrolled in this study. Matched samples of synovial membrane (SM), synovial fluid (SF) and peripheral blood (PB) were analyzed for CD3+ CD4+ CD8- T cell subsets (Th1, Th2, Th17, regulatory T cells) and activation status (CD25, CD69, CD45RO, CD45RA, CD62L) by flow cytometry...
October 28, 2018: Clinical and Experimental Immunology
J Jiao, Y Jin, M Zheng, H Zhang, M Yuan, Z Lv, W Odhiambo, X Yu, P Zhang, C Li, Y Ma, Y Ji
Diffuse large B cell lymphoma (DLBCL) is traced to a mature B malignance carrying abnormal activation-induced cytidine deaminase (AID) expression. AID activity initially focuses on deamination of cytidine to uracil to generate somatic hypermutation and class-switch recombination of the immunoglobulin (Ig), but recently it has been implicated in DNA demethylation of genes required for B cell development and proliferation in germinal center (GC). However, it has not been characterized well whether AID activity on mutation or demethylation of genes involves oncogenesis of DLBCL...
October 25, 2018: Clinical and Experimental Immunology
Ursula Fearon, Megan M Hanlon, Sarah M Wade, Jean Fletcher
Rheumatoid Arthritis is characterized by synovial proliferation, neovascularization and leukocyte extravasation leading to joint destruction and functional disability. The blood vessels in the inflamed synovium are highly dysregulated resulting in poor delivery of oxygen, this along with the increased metabolic demand of infiltrating immune cells and inflamed resident cells, results in the lack of key nutrients at the site of inflammation. In these adverse conditions synovial cells must adapt to generate sufficient energy to support their proliferation and activation status, thus switch their cell metabolism from a resting regulatory state to a highly metabolically active state...
October 25, 2018: Clinical and Experimental Immunology
Amelie Therrien, Laurence Chapuy, Marwa Bsat, Manuel Rubio, Gabriel Bernard, Elizabeth Arslanian, Katarzyna Orlicka, Audrey Weber, Benoit-Pierre Panzini, Judy Dorais, Edmond-Jean Bernard, Genevieve Soucy, Mickael Bouin, Marika Sarfati
Neutrophils are detected in inflamed colon in Crohn's disease (CD). However, whether the frequency and/or activation of circulating or gut tissue neutrophils correlate with endoscopic severity remains to be investigated. A cohort of 73 CD patients was prospectively enrolled according to endoscopic severity and treatment history. Individuals with active disease were stratified using Montreal classification. Harvey Bradshaw Index (HBI) and Simple Endoscopic score (SES-CD) were performed at the time of ileocolonoscopy...
October 22, 2018: Clinical and Experimental Immunology
E Oliver, C Pope, E Clarke, C Langton Hewer, A D Ogunniyi, J C Paton, T Mitchell, R Malley, A Finn
Pneumococcal infections cause a large global health burden, and the search for serotype-independent vaccines continues. Existing conjugate vaccines reduce nasopharyngeal colonization by target serotypes. Such mucosal effects of novel antigens may similarly be important. CD4+ Th17 cell-dependent, antibody-independent reductions in colonization and enhanced clearance have been described in mice. Here we describe the evaluation of T helper type 17 (Th17) cytokine responses to candidate pneumococcal protein vaccine antigens in human cell culture, using adenoidal and peripheral blood mononuclear cells...
October 16, 2018: Clinical and Experimental Immunology
S Xing, X Zhang, J H Liu, X Huang, P Zhou
Recent experimental strategies to reduce graft-versus-host disease (GVHD) have focused largely on modifying innate immunity. Toll-like receptor (TLR)-driven myeloid differentiation primary response 88 (MyD88)-dependent signalling pathways that initiate adaptive immune function are also critical for the pathogenesis of GVHD. This study aimed to delineate the role of host MyD88 in the development of acute GVHD following fully major histocompatibility complex-mismatched allogeneic bone marrow transplantation (BMT)...
October 14, 2018: Clinical and Experimental Immunology
Safa S Meshaal, Rabab E El Hawary, Dalia S Abd Elaziz, Alia Eldash, Radwa Alkady, Sohilla Lotfy, Andrea A Mauracher, Lennart Opitz, Jana Pachlopnik Schmid, Mirjam van der Burg, Janet Chou, Nermeen M Galal, Jeannette A Boutros, Raif Geha, Aisha M Elmarsafy
BACKGROUND: Mutations affecting Recombination Activation genes RAG1 and RAG2 are associated with variable phenotypes, depending on the residual recombinase activity. OBJECTIVE: The aim of this study is to describe a variety of clinical phenotypes in RAG-deficient patients from the highly consanguineous Egyptian population. METHODS: Thirty-one patients with RAG mutations (from 28 families) were included from 2013 to 2017. On the basis of clinical, immunologic and genetic data, patients were subdivided into three groups; classical T- B- severe combined immunodeficiency (SCID), Omenn syndrome (OS) and atypical SCID...
October 11, 2018: Clinical and Experimental Immunology
Teresa Rodriguez-Calvo
Enteroviruses have been historically associated to type 1 diabetes. Definitive proof for their implication in disease development is lacking but growing evidence suggests that they could be involved in beta cell destruction either directly by killing beta cells or indirectly, by creating an exacerbated inflammatory response in the islets, capable of attracting autoreactive T cells to the "scene of crime". Epidemiological and serological studies have been associated with the appearance of islet autoimmunity and EV RNA has been detected in prospective studies...
October 11, 2018: Clinical and Experimental Immunology
C Steen-Louws, S A Y Hartgring, J Popov-Celeketic, A P Lopes, M B M de Smet, N Eijkelkamp, F P J G Lafeber, C E Hack, J A G van Roon
OBJECTIVE: To test the capacity of a newly developed fusion protein of IL-4 and IL-10 (IL4-10 FP) to shift multiple pro-inflammatory pathways towards immune regulation, and to inhibit pro-inflammatory activity in arthritis models. METHODS: The effects of IL4-10 FP in comparison with IL-4, IL-10 and IL-4 plus IL-10 on pro- and anti-inflammatory mediators, T-cells, and Ig receptors in favour of immunoregulatory activity were studied. In addition, the capacity of IL4-10 FP to inhibit pro-inflammatory activity in ex-vivo and in-vivo arthritis models was investigated...
October 11, 2018: Clinical and Experimental Immunology
G Hodge, S Hodge, A Yeo, P Nguyen, E Hopkins, H Liu, C L Holmes-Liew, M Holmes
Immunosuppression therapies including corticosteroids fail to prevent bronchiolitis obliterans syndrome (BOS), primarily a disease of the small airways, following lung transplantation. We reported increases in steroid-resistant proinflammatory lymphocytes and their loss of histone deacetylase 2 (HDAC2), an important mediator of steroid action, in the blood of stable lung transplant recipients. We noted similar increases in the steroid-resistant lymphocytes in both the blood and small airways in BOS compared with the large airways...
October 10, 2018: Clinical and Experimental Immunology
X Hu, J Tang, X Hu, P Bao, J Pan, Y Ou, W Deng, Y Liang
In this study, we aimed to explore the effects of imatinib on the proliferation of rheumatoid arthritis synovial cell (RA-FLS) and inflammatory responses by regulating CSF1R. Differential genes were screened via microarray analysis, followed by being analysed through the weighted co-expression network (WGCNA) network, that included module and cluster analysis. The relationship between imatinib and genes was visualized using the Search Tool for the Retrieval of Interacting Genes (STITCH) database. Expressions of mRNA and protein were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, respectively...
October 3, 2018: Clinical and Experimental Immunology
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