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Systemic autoimmunity

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https://www.readbyqxmd.com/read/28642817/cerebral-vasculitis-mimicking-intracranial-metastatic-progression-of-lung-cancer-during-pd-1-blockade
#1
Heinz Läubli, Jürgen Hench, Michal Stanczak, Ingmar Heijnen, Alexandros Papachristofilou, Stephan Frank, Alfred Zippelius, Frank Stenner-Liewen
BACKGROUND: Stimulation of the immune system by targeting the PD-1/PD-L1 pathway can result in activation of anti-tumor immunity. Besides its clinical benefit immune checkpoint therapy leads to significant immune-related adverse events (irAEs). Some rare irAEs are not well described yet but are critical in patient management. CASE PRESENTATION: Here, we describe a case of autoimmune cerebral vasculitis/encephalitis after PD-1 inhibitor treatment for metastatic adenocarcinoma of the lung...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28642759/biodistribution-and-efficacy-of-human-adipose-derived-mesenchymal-stem-cells-following-intranodal-administration-in-experimental-colitis
#2
Mercedes Lopez-Santalla, Pablo Mancheño-Corvo, Amelia Escolano, Ramon Menta, Olga DelaRosa, Jose Luis Abad, Dirk Büscher, Juan M Redondo, Juan A Bueren, Wilfried Dalemans, Eleuterio Lombardo, Marina I Garin
Mesenchymal stem cells (MSCs) have a large potential in cell therapy for treatment of inflammatory and autoimmune diseases, thanks to their immunomodulatory properties. The encouraging results in animal models have initiated the translation of MSC therapy to clinical trials. In cell therapy protocols with MSCs, administered intravenously, several studies have shown that a small proportion of infused MSCs can traffic to the draining lymph nodes (LNs). This is accompanied with an increase of different types of regulatory immune cells in the LNs, suggesting the importance of migration of MSCs to the LNs in order to contribute to immunomodulatory response...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28642030/cyclic-mog35-55-ameliorates-clinical-and-neuropathological-features-of-experimental-autoimmune-encephalomyelitis
#3
Athanasios Lourbopoulos, George Deraos, Minos-Timotheos Matsoukas, Olga Touloumi, Aggeliki Giannakopoulou, Hubert Kalbacher, Nikolaos Grigoriadis, Vasso Apostolopoulos, John Matsoukas
EAE is induced to susceptible mice using linear peptides of myelin proteins of the central nervous system. Specific peptide motifs within the peptide-binding groove of the MHC peptide-complex determines the affinity of the peptide in each animal and the consequent T-cell receptor recognition and activation of the cell. Altered peptide ligand (APL) vaccination is a novel approach based on an effort to induce T-cell tolerance or alter cytokine profile from pro-inflammatory to anti-inflammatory. In the present study we synthesized the MOG35-55 peptide and altered its 3-dimensional conformation to make it a cyclic one (c-MOG35-55)...
June 7, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28641866/t-bet-expressing-b-cells-novel-target-for-autoimmune-therapies
#4
Anatoly V Rubtsov, Philippa Marrack, Kira Rubtsova
Autoimmune diseases affect more than 23.5million Americans. Traditional therapies for autoimmune diseases involve immunosuppressive drugs that globally dampen immune responses or target and kill large populations of normal immune cells. Both approaches lead to severe dysfunction of the immune system increasing the risk of infections and cancer. Therefore, a more targeted approach, modulating only the pathogenic autoimmune response, would be tremendously beneficial for autoimmune patients. However, only some novel targets involved in pathogenic autoimmune response have been discovered and it is likely that more remain, currently unknown...
May 23, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28639951/metabolic-abnormalities-and-oxidative-stress-in-lupus
#5
Yaima L Lightfoot, Luz P Blanco, Mariana J Kaplan
PURPOSE OF REVIEW: Upon antigen exposure, immune cells rely on cell-specific metabolic pathways to mount an efficient immune response. In autoimmunity, failure in critical metabolic checkpoints may lead to immune cell hyperactivation and tissue damage. Oxidative stress in autoimmune patients can also contribute to immune dysregulation and injury to the host. Recent insights into the immune cell metabolism signatures, specifically associated with systemic lupus erythematosus (SLE) and the consequences of heightened oxidative stress in patients, are discussed herein...
July 20, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28639945/pulmonary-arterial-hemodynamic-assessment-by-a-novel-index-in-systemic-lupus-erythematosus-patients-pulmonary-pulse-transit-time
#6
Tolga Han Efe, Mehmet Doğan, Cem Özişler, Tolga Çimen, Mehmet Ali Felekoğlu, Ahmet Göktuğ Ertem, Engin Algül, Sadık Açıkel
OBJECTIVE: Systemic lupus erythematosus (SLE) is a chronic, inflammatory, and autoimmune connective tissue disease. One of the leading causes of mortality among SLE patients is pulmonary hypertension. The aim of this study was to evaluate the association between echocardiographic findings, including the pulmonary pulse transit time and pulmonary hypertension parameters, in SLE patients. METHODS: Thirty SLE patients (aged 39.9±11 years, 28 females) as the study group and 34 age- and sex-matched healthy volunteers (aged 37...
June 22, 2017: Anatolian Journal of Cardiology
https://www.readbyqxmd.com/read/28639716/expression-of-the-autoantigen-trim33-tif1%C3%AE-in-skin-and-muscle-of-patients-with-dermatomyositis-is-upregulated-together-with-markers-of-cellular-stress
#7
B Scholtissek, S Ferring-Schmitt, J Maier, J Wenzel
Dermatomyositis (DM) is an autoimmune disorder associated with a dysregulation of immune homeostasis of both the innate and adaptive immune system. Earlier data suggested that these two arms of the immune system interconnect in DM. In the current study, we analysed the association of autoantigen expression [adaptive system components: Mi2, transcriptional intermediary factor (TIF)1γ, small ubiquitin-like modifier 1 activating enzyme subunit (SAE)1, melanoma differentiation-associated protein (MDA)5] with markers of cellular stress (innate system components: MxA, p53) in skin and muscle (immunohistology and gene expression data, respectively)...
June 22, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28639412/the-role-of-microrna-5196-in-the-pathogenesis-of-systemic-sclerosis
#8
Marzena Ciechomska, Patryk Zarecki, Michal Merdas, Jerzy Swierkot, Ewa Morgiel, Piotr Wiland, Wlodzimierz Maslinski, Katarzyna Bogunia-Kubik
BACKGROUND: Systemic sclerosis (SSc) is a chronic autoimmune disease characterised by tissue fibrosis and immune abnormalities. Recent evidence suggests that activated circulating monocytes from SSc patients play an important role in early stages of SSc pathogenesis due to enhanced expression of tissue inhibitor of metalloproteinases 1 (TIMP-1), IL-8 and reactive oxygen species (ROS) induction. However, the exact factors that contribute to chronic inflammation and subsequently fibrosis progression are still unknown...
June 21, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28639207/the-cell-biology-of-the-thyroid-disrupting-mechanism-of-dichlorodiphenyltrichloroethane-ddt
#9
REVIEW
M Rossi, A R Taddei, I Fasciani, R Maggio, F Giorgi
OBJECTIVE: Dichlorodiphenyltrichloroethane (DDT) is an organochlorine known for its pesticide properties and for its negative effects on human health. It was banned in most countries for its toxicity to the endocrine system, but due to its persistence at clinically relevant concentrations in both soil and animal tissues, DDT is still linked to several health and social problems. METHODS: We have previously shown that DDT exposure is causally related to the extracellular release of vesicular organelles such as microvesicles and/or exosomes by using immunocytochemistry with gold-tagged antibodies and various fluorescent membrane markers...
June 21, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28638382/expanding-role-of-t-cells-in-human-autoimmune-diseases-of-the-central-nervous-system
#10
REVIEW
Deepti Pilli, Alicia Zou, Fiona Tea, Russell C Dale, Fabienne Brilot
It is being increasingly recognized that a dysregulation of the immune system plays a vital role in neurological disorders and shapes the treatment of the disease. Aberrant T cell responses, in particular, are key in driving autoimmunity and have been traditionally associated with multiple sclerosis. Yet, it is evident that there are other neurological diseases in which autoreactive T cells have an active role in pathogenesis. In this review, we report on the recent progress in profiling and assessing the functionality of autoreactive T cells in central nervous system (CNS) autoimmune disorders that are currently postulated to be primarily T cell driven...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28637902/tgf-%C3%AE-1-suppresses-il-33-induced-mast-cell-function
#11
Victor S Ndaw, Daniel Abebayehu, Andrew J Spence, Patrick A Paez, E Motunrayo Kolawole, Marcela T Taruselli, Heather L Caslin, Alena P Chumanevich, Anuya Paranjape, Bianca Baker, Brian O Barnstein, Tamara T Haque, Kasalina N Kiwanuka, Carole A Oskeritzian, John J Ryan
TGF-β1 is involved in many pathological conditions, including autoimmune disorders, cancer, and cardiovascular and allergic diseases. We have previously found that TGF-β1 can suppress IgE-mediated mast cell activation of human and mouse mast cells. IL-33 is a member of the IL-1 family capable of inducing mast cell responses and enhancing IgE-mediated activation. In this study, we investigated the effects of TGF-β on IL-33-mediated mast cell activation. Bone marrow-derived mast cells cultured in TGF-β1, β2, or β3 showed reduced IL-33-mediated production of TNF, IL-6, IL-13, and MCP-1 in a concentration-dependent manner...
June 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28637725/filling-the-gaps-in-sards-research-collection-and-linkage-of-administrative-health-data-and-self-reported-survey-data-for-a-general-population-based-cohort-of-individuals-with-and-without-diagnoses-of-systemic-autoimmune-rheumatic-disease-sards-from-british
#12
Natalie McCormick, Kathryn Reimer, Ali Famouri, Carlo A Marra, J Antonio Aviña-Zubieta
PURPOSE: Systemic autoimmune rheumatic diseases (SARDs) are a group of debilitating autoimmune diseases, including systemic lupus erythematosus and related disorders. Assessing the healthcare and economic burden of SARDs has been challenging: while administrative databases can be used to determine healthcare utilisation and costs with minimal selection and recall bias, other health, sociodemographic and economic data have typically been sourced from highly selected, clinic-based cohorts...
June 21, 2017: BMJ Open
https://www.readbyqxmd.com/read/28637619/practical-considerations-for-diagnosis-and-management-of-patients-and-carriers
#13
REVIEW
Charlotte M Niemeyer, Cristina Mecucci
Newly diagnosed children and adults with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) need to be screened for presence of a genetic predisposition syndrome because the information on the genetic status is likely to influence clinical care and management of the patient and the family. Scenarios in which genetic counseling is advised include presence of a mutation on somatic screen that can be associated with a germline predisposition, hematologic or cytogenetic characteristics suggestive of an underlying susceptibility syndrome, non-hematological phenotype suspicious for a familial condition, history of previous malignancy, or a family history of cancer, cytopenia, autoimmunity, or organ-system manifestation fitting a predisposition syndrome...
April 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28636961/myeloid-cells-in-the-central-nervous-system
#14
REVIEW
Jasmin Herz, Anthony J Filiano, Ashtyn Smith, Nir Yogev, Jonathan Kipnis
The central nervous system (CNS) and its meningeal coverings accommodate a diverse myeloid compartment that includes parenchymal microglia and perivascular macrophages, as well as choroid plexus and meningeal macrophages, dendritic cells, and granulocytes. These myeloid populations enjoy an intimate relationship with the CNS, where they play an essential role in both health and disease. Although the importance of these cells is clearly recognized, their exact function in the CNS continues to be explored. Here, we review the subsets of myeloid cells that inhabit the parenchyma, meninges, and choroid plexus and discuss their roles in CNS homeostasis...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636960/mechanisms-and-therapeutic-relevance-of-neuro-immune-communication
#15
REVIEW
Sangeeta S Chavan, Valentin A Pavlov, Kevin J Tracey
Active research at the frontiers of immunology and neuroscience has identified multiple points of interaction and communication between the immune system and the nervous system. Immune cell activation stimulates neuronal circuits that regulate innate and adaptive immunity. Molecular mechanistic insights into the inflammatory reflex and other neuro-immune interactions have greatly advanced our understanding of immunity and identified new therapeutic possibilities in inflammatory and autoimmune diseases. Recent successful clinical trials using bioelectronic devices that modulate the inflammatory reflex to significantly ameliorate rheumatoid arthritis and inflammatory bowel disease provide a path for using electrons as a therapeutic modality for targeting molecular mechanisms of immunity...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636952/human-leukocyte-antigen-f-presents-peptides-and-regulates-immunity-through-interactions-with-nk-cell-receptors
#16
Charles L Dulberger, Curtis P McMurtrey, Angelique Hölzemer, Karlynn E Neu, Victor Liu, Adriana M Steinbach, Wilfredo F Garcia-Beltran, Michael Sulak, Bana Jabri, Vincent J Lynch, Marcus Altfeld, William H Hildebrand, Erin J Adams
Evidence is mounting that the major histocompatibility complex (MHC) molecule HLA-F (human leukocyte antigen F) regulates the immune system in pregnancy, infection, and autoimmunity by signaling through NK cell receptors (NKRs). We present structural, biochemical, and evolutionary analyses demonstrating that HLA-F presents peptides of unconventional length dictated by a newly arisen mutation (R62W) that has produced an open-ended groove accommodating particularly long peptides. Compared to empty HLA-F open conformers (OCs), HLA-F tetramers bound with human-derived peptides differentially stained leukocytes, suggesting peptide-dependent engagement...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636654/characterization-of-human-fcrl4-positive-b-cells
#17
Michel Jourdan, Nicolas Robert, Maïlys Cren, Coraline Thibaut, Christophe Duperray, Alboukadel Kassambara, Michel Cogné, Karin Tarte, Bernard Klein, Jérôme Moreaux
FCRL4 is an immunoregulatory receptor that belongs to the Fc receptor-like (FCRL) family. In healthy individuals, FCRL4 is specifically expressed by memory B cells (MBCs) localized in sub-epithelial regions of lymphoid tissues. Expansion of FCRL4+ B cells has been observed in blood and other tissues in various infectious and autoimmune disorders. Currently, the mechanisms involved in pathological FCRL4+ B cell generation are actively studied, but they remain elusive. As in vivo FCRL4+ cells are difficult to access and to isolate, here we developed a culture system to generate in vitro FCRL4+ B cells from purified MBCs upon stimulation with soluble CD40 ligand and/or CpG DNA to mimic T-cell dependent and/or T-cell independent activation, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28635319/a-case-of-topical-ruxolitinib-treatment-failure-in-alopecia-areata
#18
Maya Deeb, Renée A Beach
Alopecia areata (AA) is an autoimmune-mediated, nonscarring form of hair loss. Despite its prevalence, current management options are limited, especially when the disease has progressed to alopecia totalis (AT) or alopecia universalis (AU). Recent evidence that janus kinase (JAK) signaling contributes to AA pathogenesis prompted the investigation of JAK inhibitors such as tofacitinib and ruxolitinib as possible oral treatments. However, the potential for significant adverse effects with systemic JAK inhibition makes local administration a more attractive option...
June 1, 2017: Journal of Cutaneous Medicine and Surgery
https://www.readbyqxmd.com/read/28634006/testosterone-differentially-affects-t-cells-and-neurons-in-murine-and-human-models-of-neuroinflammation-and-neurodegeneration
#19
Megan G Massa, Christina David, Stefanie Jörg, Johannes Berg, Barbara Gisevius, Sarah Hirschberg, Ralf A Linker, Ralf Gold, Aiden Haghikia
The high female-to-male sex ratio of multiple sclerosis (MS) prevalence has continuously confounded researchers, especially in light of male patients' accelerated disease course at later stages of MS. Although multiple studies have concentrated on estrogenic mechanisms of disease modulation, fairly little attention has been paid to androgenic effects in a female system, and even fewer studies have attempted to dissociate hormonal effects on the neurodegenerative and neuroinflammatory processes of MS. Herein, we demonstrate the differential effects of hormone treatment on the acute inflammatory and chronic neurodegenerative phases of murine experimental autoimmune encephalomyelitis...
July 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28632714/the-multiple-pathways-to-autoimmunity
#20
REVIEW
Argyrios N Theofilopoulos, Dwight H Kono, Roberto Baccala
Efforts to understand autoimmunity have been pursued relentlessly for several decades. It has become apparent that the immune system evolved multiple mechanisms for controlling self-reactivity, and defects in one or more of these mechanisms can lead to a breakdown of tolerance. Among the multitude of lesions associated with disease, the most common seem to affect peripheral tolerance rather than central tolerance. The initial trigger for both systemic autoimmune disorders and organ-specific autoimmune disorders probably involves the recognition of self or foreign molecules, especially nucleic acids, by innate sensors...
June 20, 2017: Nature Immunology
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