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mechanism of anca

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https://www.readbyqxmd.com/read/29141676/platelets-are-activated-in-anca-associated-vasculitis-via-thrombin-pars-pathway-and-can-activate-the-alternative-complement-pathway
#1
Di Miao, Dan-Yang Li, Min Chen, Ming-Hui Zhao
BACKGROUND: In this study, we investigated the mechanism of platelet activation in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), as well as the activation of the alternative complement pathway by platelets in AAV. METHODS: CD62P and platelet-leukocyte aggregates in AAV patients were tested by flow cytometry. Platelets were stimulated by plasma from active AAV patients. The effect of the thrombin-protease-activated receptors (PARs) pathway was evaluated by blocking thrombin or PAR1 antagonists...
November 15, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29128969/in-vasculitis-of-small-muscular-arteries-activation-of-vessel-infiltrating-cd8-t-cells-seems-to-be-antigen-independent
#2
Mikiko Kobayashi, Eisaku Ogawa, Ryuhei Okuyama, Hiroyuki Kanno
The etiology of polyarteritis nodosa (PAN) and localized PAN is still unknown, although a T cell-mediated immune mechanism has been considered. CD8 T cells participate not only in the antigen-dependent adaptive immune system, but also in the antigen-independent innate immune system. Non-antigen-activated CD8 T cells express a unique phenotype: granzyme B (GrB) positive /CD25 negative /programmed death-1 (PD-1) negative. The aims of this study were to assess the participation of T cells, especially innate CD8 T cells, in the development of vasculitis...
November 11, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29106439/increased-diastolic-blood-pressure-is-associated-with-mri-biomarkers-of-dementia-related-brain-pathology-in-normative-ageing
#3
Christopher J McNeil, Phyo Kyaw Myint, Anca-Larisa Sandu, John F Potter, Roger Staff, Lawrence J Whalley, Alison D Murray
Background: hypertension is a risk for brain ageing, but the mechanisms underlying this effect remain unclear. Magnetic resonance imaging (MRI) detected biomarkers of brain ageing include white matter hyperintensities (WMHs), a marker of cerebrovascular disease, and hippocampal volume, a marker of Alzheimer's disease pathology. Objective: to examine relationships between blood pressure (BP) components and brain pathology in older adults. Subjects: two hundred and twenty-seven members of the Aberdeen 1936 Birth Cohort between ages 64 and 68 years...
July 4, 2017: Age and Ageing
https://www.readbyqxmd.com/read/29100671/-nettling-the-host-breaking-of-tolerance-in-chronic-inflammation-and-chronic-infection
#4
REVIEW
Sladjana Skopelja-Gardner, Jonathan D Jones, William F C Rigby
How and why we break tolerance to self-proteins still remains a largely unanswered question. Neutrophils have been identified as a rich source of autoantigens in a wide array of autoimmune diseases that arise as a consequence of different environmental and genetic factors, e.g. rheumatoid arthritis (RA), lupus, vasculitis, cystic fibrosis (CF) etc. Specifically, neutrophil extracellular trap (NET) formation has been identified as a link between innate and adaptive immune responses in autoimmunity. Autoantigens including neutrophil granular proteins (targeted by anti-neutrophil cytoplasmic antibodies, ANCA) as well as post-translationally modified proteins, i...
October 31, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29082297/distinct-pathogenesis-in-nonsystemic-vasculitic-neuropathy-and-microscopic-polyangiitis
#5
Mie Takahashi, Haruki Koike, Shohei Ikeda, Yuichi Kawagashira, Masahiro Iijima, Atsushi Hashizume, Masahisa Katsuno, Gen Sobue
OBJECTIVE: To investigate the mechanisms of vasculitis in nonsystemic vasculitic neuropathy (NSVN) and microscopic polyangiitis (MPA), focusing on complement- and antineutrophil cytoplasmic antibody (ANCA)-associated pathogenesis. METHODS: Sural nerve biopsy specimens taken from twenty-four patients with NSVN and 37 with MPA-associated neuropathy (MPAN) were examined. Twenty-two patients in the MPAN group tested positive for ANCA. RESULTS: Immunostaining for complement component C3d deposition showed more frequent positive staining of epineurial small vessels in NSVN than in MPAN (p = 0...
November 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/29078325/necroptosis-controls-net-generation-and-mediates-complement-activation-endothelial-damage-and-autoimmune-vasculitis
#6
Adrian Schreiber, Anthony Rousselle, Jan Ulrich Becker, Anne von Mässenhausen, Andreas Linkermann, Ralph Kettritz
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) constitutes life-threatening autoimmune diseases affecting every organ, including the kidneys, where they cause necrotizing crescentic glomerulonephritis. ANCA activates neutrophils and activated neutrophils damage the endothelium, leading to vascular inflammation and necrosis. Better understanding of neutrophil-mediated AAV disease mechanisms may reveal novel treatment strategies. Here we report that ANCA induces neutrophil extracellular traps (NETs) via receptor-interacting protein kinase (RIPK) 1/3- and mixed-lineage kinase domain-like (MLKL)-dependent necroptosis...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29061248/involvement-of-the-peripheral-nervous-system-in-polyarteritis-nodosa-and-antineutrophil-cytoplasmic-antibodies-associated-vasculitis
#7
REVIEW
John B Imboden
Peripheral nerve involvement is common in polyarteritis nodosa and the antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides. The underlying mechanism is arteritis of the vasa nervorum, leading to ischemic neuropathy. The classic presentation is stepwise involvement of peripheral nerves with ongoing antecedent constitutional symptoms. This article reviews the pathologic findings, clinical syndromes, diagnosis, and treatment of ANCA-associated vasculitides.
November 2017: Rheumatic Diseases Clinics of North America
https://www.readbyqxmd.com/read/29055004/stat4-regulates-the-cd8-regulatory-t-cell-t-follicular-helper-cell-axis-and-promotes-atherogenesis-in-insulin-resistant-ldlr-mice
#8
Parésa L Taghavie-Moghadam, Tayab C Waseem, Julian Hattler, Lindsey M Glenn, Anca D Dobrian, Mark H Kaplan, Yi Yang, Roza Nurieva, Jerry L Nadler, Elena V Galkina
The metabolic syndrome and diabetic conditions support atherosclerosis, but the exact mechanisms for accelerated atherogenesis remain unclear. Although the proinflammatory role of STAT4 in atherosclerosis and diet-induced insulin resistance (IR) was recently established, the impact of STAT4 on atherogenesis in conditions of IR is not known. In this study, we generated Stat4(-/-)Ldlr(-/-) mice that were fed a diabetogenic diet with added cholesterol (DDC). DDC-fed Stat4(-/-)Ldlr(-/-) mice demonstrated improved glucose tolerance, insulin sensitivity, and a 36% reduction in atherosclerosis compared with Ldlr(-/-) controls...
November 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29043147/a-case-report-of-paraproteinemia-associated-pauci-immune-glomerulonephritis-a-new-form-of-monoclonal-gammopathy-of-renal-significance
#9
Robert Rope, Neeraja Kambham, Neiha Arora
BACKGROUND: Renal disease associated with paraproteinemias is classically predicated upon pathologic paraprotein deposition in the kidney. However, growing evidence suggests that paraproteins may be able to systemically activate complement or neutrophils to drive renal damage. This may provide an alternative pathologic mechanism for renal injury in rare cases. CASE REPORT: We report a case of a patient with crescentic pauci-immune glomerulonephritis presenting with rapidly progressive renal failure, polyarthropathy, and a purpuric rash in association with a monoclonal immunoglobulin G κ-light-chain producing multiple myeloma...
2017: Clin Nephrol Case Stud
https://www.readbyqxmd.com/read/29042750/current-perspective-on-rituximab-in-rheumatic-diseases
#10
REVIEW
Tommaso Schioppo, Francesca Ingegnoli
The steadily increasing knowledge regarding pathogenetic mechanisms in autoimmune rheumatic diseases has paved the way to different therapeutic approaches. In particular, the market entry of biologics has dramatically modified the natural history of rheumatic chronic inflammatory diseases with a meaningful impact on patients' quality of life. Among the wide spectrum of available biological treatments, rituximab (RTX), first used in the treatment of non-Hodgkin's lymphoma, was later approved for rheumatoid arthritis and anti-neutrophil cytoplasmic antibodies-associated vasculitis...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28994331/evaluating-the-involvement-of-cerebral-microvascular-endothelial-na-k-atpase-and-na-k-2cl-co-transporter-in-electrolyte-fluxes-in-an-in%C3%A2-vitro-blood-brain-barrier-model-of-dehydration
#11
Kasper Lykke, Mette Assentoft, Sofie Hørlyck, Hans Cc Helms, Anca Stoica, Trine L Toft-Bertelsen, Katerina Tritsaris, Frederik Vilhardt, Birger Brodin, Nanna MacAulay
The blood-brain barrier (BBB) is involved in brain water and salt homeostasis. Blood osmolarity increases during dehydration and water is osmotically extracted from the brain. The loss of water is less than expected from pure osmotic forces, due to brain electrolyte accumulation. Although the underlying molecular mechanisms are unresolved, the current model suggests the luminally expressed Na(+)-K(+)-2Cl(-) co-transporter 1 (NKCC1) as a key component, while the role of the Na(+)/K(+)-ATPase remains uninvestigated...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28959657/cyp-polymorphisms-and-pathological-conditions-related-to-chronic-exposure-to-organochlorine-pesticides
#12
REVIEW
Anca Oana Docea, Loukia Vassilopoulou, Domniki Fragou, Andreea Letitia Arsene, Concettina Fenga, Leda Kovatsi, Dimitrios Petrakis, Valerii N Rakitskii, Alexander E Nosyrev, Boris N Izotov, Kirill S Golokhvast, Alexander M Zakharenko, Antonis Vakis, Christina Tsitsimpikou, Nikolaos Drakoulis
The association between genetic variations in the cytochrome P450 (CYP) family genes and pathological conditions related to long-term exposure to organochlorine compounds (OCs) deserves further elucidation. OCs are persistent organic pollutants with bioaccumulative and lipophilic characteristics. They can act as endocrine disruptors and perturb cellular mechanisms. Prolonged exposure to OCs has been associated with different pathological manifestations. CYP genes are responsible for transcribing enzymes essential in xenobiotic metabolism...
2017: Toxicology Reports
https://www.readbyqxmd.com/read/28957963/an-update-on-the-role-of-epigenetics-in-systemic-vasculitis
#13
Patrick Coit, Haner Direskeneli, Amr H Sawalha
PURPOSE OF REVIEW: The purpose of this review is to discuss recent observations of epigenetic changes related to the complex pathogenesis of systemic vasculitides and their contribution to the field. RECENT FINDINGS: There have been new observations of epigenetic changes in vasculitis and their potential role in disease pathogenesis in antineutrophil cytoplasmic antibody-associated vasculitis, giant-cell arteritis, Kawasaki disease, Behçet's disease, and IgA vasculitis...
September 27, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28957962/neutrophil-extracellular-traps-in-vasculitis-friend-or-foe
#14
Daniel Söderberg, Mårten Segelmark
PURPOSE OF REVIEW: Neutrophil extracellular traps (NETs) can be found at the sites of vascular lesions and in the circulation of patients with active small vessel vasculitis. Neutrophils from vasculitis patients release more NETs in vitro, and NETs have properties that can harm the vasculature both directly and indirectly. There are several ways to interfere with NET formation, which open for new therapeutic options. However, there are several types of NETs and different mechanisms of NET formation, and these might have different effects on inflammation...
September 27, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28933419/the-cardiovascular-effects-of-cocoa-polyphenols-an-overview
#15
REVIEW
Ana Clara Aprotosoaie, Anca Miron, Adriana Trifan, Vlad Simon Luca, Irina-Iuliana Costache
Cocoa is a rich source of high-quality antioxidant polyphenols. They comprise mainly catechins (29%-38% of total polyphenols), anthocyanins (4% of total polyphenols) and proanthocyanidins (58%-65% of total polyphenols). A growing body of experimental and epidemiological evidence highlights that the intake of cocoa polyphenols may reduce the risk of cardiovascular events. Beyond antioxidant properties, cocoa polyphenols exert blood pressure lowering activity, antiplatelet, anti-inflammatory, metabolic and anti-atherosclerotic effects, and also improve endothelial function...
December 17, 2016: Diseases (Basel)
https://www.readbyqxmd.com/read/28919990/pharmacological-targeting-of-peptidylarginine-deiminase-4-prevents-cancer-associated-kidney-injury-in-mice
#16
Jessica Cedervall, Anca Dragomir, Falk Saupe, Yanyu Zhang, Johan Ärnlöv, Erik Larsson, Anna Dimberg, Anders Larsson, Anna-Karin Olsson
Renal insufficiency is a frequent cancer-associated problem affecting more than half of all cancer patients at the time of diagnosis. To minimize nephrotoxic effects the dosage of anticancer drugs are reduced in these patients, leading to sub-optimal treatment efficacy. Despite the severity of this cancer-associated pathology, the molecular mechanisms, as well as therapeutic options, are still largely lacking. We here show that formation of intravascular tumor-induced neutrophil extracellular traps (NETs) is a cause of kidney injury in tumor-bearing mice...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28899799/neutrophil-extracellular-traps-nets-in-autoimmune-diseases-a-comprehensive-review
#17
REVIEW
Keum Hwa Lee, Andreas Kronbichler, David Duck-Young Park, YoungMin Park, Hanwool Moon, Hyungdo Kim, Jun Hyug Choi, YoungSeo Choi, Songjoo Shim, Il Suk Lyu, Byung Hwan Yun, Yeonseung Han, Donghee Lee, Sang Yoon Lee, Byung Hun Yoo, Kyung Hwan Lee, Tai Lim Kim, Heonki Kim, Joo Sung Shim, Wonseok Nam, Heesung So, SooYeon Choi, Sangmok Lee, Jae Il Shin
Neutrophil extracellular traps (NETs) are fibrous networks which protrude from the membranes of activated neutrophils. NETs are found in a variety of conditions such as infection, malignancy, atherosclerosis, and autoimmune diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV), psoriasis, and gout. Studies suggest that an imbalance between "NETosis," which is a process by which NETs are formed, and NET degradation may be associated with autoimmune diseases...
September 9, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28863790/anca-associated-vasculitis-pathogenesis-models-and-preclinical-testing
#18
REVIEW
Holly L Hutton, Stephen R Holdsworth, A Richard Kitching
Our understanding of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis has developed greatly since the discovery of ANCA, directed against neutrophil components, in 1982. Observations in human disease, and increasingly sophisticated studies in vitro and in rodent models in vivo, have allowed a nuanced understanding of many aspects of the immunopathogenesis of disease, including the significance of ANCA as a diagnostic and monitoring tool as well as a mediator of microvascular injury. The mechanisms of leukocyte recruitment and tissue injury, and the role of T cells increasingly are understood...
September 2017: Seminars in Nephrology
https://www.readbyqxmd.com/read/28852481/infectious-complications-of-rituximab-therapy-in-renal-disease
#19
Andrew Nixon, Leanne Ogden, Alexander Woywodt, Ajay Dhaygude
Rituximab, an anti-CD20 monoclonal antibody, was originally used to treat B-cell malignancies. Its use has significantly increased in recent years, as it is now also used to treat a variety of autoimmune diseases including rheumatoid arthritis and ANCA-associated vasculitis (AAV). Initial studies suggested that the adverse effects of rituximab were minimal. Though the risk of malignancy with rituximab-based immunosuppressive regimens appears similar to that of the general population, there are now concerns regarding the risk of infectious complications...
August 2017: Clinical Kidney Journal
https://www.readbyqxmd.com/read/28829051/dopamine-transporter-and-reward-anticipation-in-a-dimensional-perspective-a-multimodal-brain-imaging-study
#20
Manon Dubol, Christian Trichard, Claire Leroy, Anca-Larisa Sandu, Mehdi Rahim, Bernard Granger, Eleni T Tzavara, Laurent Karila, Jean-Luc Martinot, Eric Artiges
Dopamine function and reward processing are highly interrelated and involve common brain regions afferent to the Nucleus Accumbens, within the mesolimbic pathway. While dopamine function and reward system neural activity are impaired in most psychiatric disorders, it is unknown if alterations in the dopamine system underlie variations in reward processing across a continuum encompassing health and these disorders. We explored the relationship between dopamine function and neural activity during reward anticipation in twenty-seven participants including healthy volunteers and psychiatric patients with schizophrenia, depression or cocaine addiction, using functional Magnetic Resonance Imaging (fMRI) and Positron Emission Tomography (PET) multimodal imaging with a voxel-based statistical approach...
August 22, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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