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Alternative complement pathway

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https://www.readbyqxmd.com/read/29686679/sparking-fire-under-the-skin-answers-from-the-association-of-complement-genes-with-pemphigus-foliaceus
#1
Valéria Bumiller-Bini, Gabriel Adelman Cipolla, Rodrigo Coutinho de Almeida, Maria Luiza Petzl-Erler, Danillo Gardenal Augusto, Angelica Beate Winter Boldt
Skin blisters of pemphigus foliaceus (PF) present concomitant deposition of autoantibodies and components of the complement system (CS), whose gene polymorphisms are associated with susceptibility to different autoimmune diseases. To investigate these in PF, we evaluated 992 single-nucleotide polymorphisms (SNPs) of 44 CS genes, genotyped through microarray hybridization in 229 PF patients and 194 controls. After excluding SNPs with minor allele frequency <1%, out of Hardy-Weinberg equilibrium in controls or in strong linkage disequilibrium ( r 2  ≥ 0...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29686675/pathogenetic-and-clinical-aspects-of-anti-neutrophil-cytoplasmic-autoantibody-associated-vasculitides
#2
REVIEW
Peter Lamprecht, Anja Kerstein, Sebastian Klapa, Susanne Schinke, Christian M Karsten, Xinhua Yu, Marc Ehlers, Jörg T Epplen, Konstanze Holl-Ulrich, Thorsten Wiech, Kathrin Kalies, Tanja Lange, Martin Laudien, Tamas Laskay, Timo Gemoll, Udo Schumacher, Sebastian Ullrich, Hauke Busch, Saleh Ibrahim, Nicole Fischer, Katrin Hasselbacher, Ralph Pries, Frank Petersen, Gesche Weppner, Rudolf Manz, Jens Y Humrich, Relana Nieberding, Gabriela Riemekasten, Antje Müller
Anti-neutrophil cytoplasmic autoantibodies (ANCA) targeting proteinase 3 (PR3) and myeloperoxidase expressed by innate immune cells (neutrophils and monocytes) are salient diagnostic and pathogenic features of small vessel vasculitis, comprising granulomatosis with polyangiitis (GPA), microscopic polyangiitis, and eosinophilic GPA. Genetic studies suggest that ANCA-associated vasculitides (AAV) constitute separate diseases, which share common immunological and pathological features, but are otherwise heterogeneous...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29678228/analyzing-complement-activity-in-the-serum-and-body-homogenates-of-different-fish-species-using-rabbit-and-sheep-red-blood-cells
#3
Sagar Nayak, Isabel Portugal, Dina Zilberg
Alternative complement activity was determined in whole body homogenates (WBHs) and serum samples of different fish species, by measuring the amount of sample that induces 50% hemolysis of red blood cells using the ACH50 assay (Alternative Complement pathway Hemolytic activity). Values of ACH50 obtained for serum samples were about two-fold higher when using rabbit red blood cells (RRBC), as compared to sheep red blood cells (SRBC). The increase in ACH50 when using RRBCs for WBH samples was 28, 7 and 4 folds for guppy, molly and zebrafish, respectively...
May 2018: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/29675946/plasma-proteomics-identifies-a-chemokine-storm-in-idiopathic-multicentric-castleman-disease
#4
Sheila K Pierson, Aaron J Stonestrom, Dustin Shilling, Jason Ruth, Christopher S Nabel, Amrit Singh, Yue Ren, Katie Stone, Hongzhe Li, Frits van Rhee, David C Fajgenbaum
Human Herpesvirus-8 (HHV-8)-negative/idiopathic multicentric Castleman disease (iMCD) is a poorly understood disease involving polyclonal lymphoproliferation with dysmorphic germinal centers, constitutional symptoms, and multi-organ failure. Patients can experience thrombocytopenia, anasarca, reticulin fibrosis, renal dysfunction, organomegaly, and normal immunoglobulin levels, - iMCD-TAFRO. Others experience thrombocytosis, milder effusions, and hypergammaglobulinemia, -iMCD-Not Otherwise Specified (iMCD-NOS)...
April 20, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29670616/overactivity-of-alternative-pathway-convertases-in-patients-with-complement-mediated-renal-diseases
#5
Marloes A H M Michels, Nicole C A J van de Kar, Marcin Okrój, Anna M Blom, Sanne A W van Kraaij, Elena B Volokhina, Lambertus P W J van den Heuvel
Overactivation of the alternative pathway of the complement system is associated with the renal diseases atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G). C3 nephritic factors (C3NeF) play an important role in C3G pathogenesis by stabilizing the key enzymatic complex of complement, the C3 convertase. However, the reliability of assays detecting these autoantibodies is limited. Therefore, in this study, we validated and optimized a prototype hemolytic method for robust detection and characterization of factors causing convertase overactivity in large patient cohorts...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29666752/pathways-of-topological-rank-analysis-potra-a-novel-method-to-detect-pathways-involved-in-hepatocellular-carcinoma
#6
Chaoxing Li, Li Liu, Valentin Dinu
Complex diseases such as cancer are usually the result of a combination of environmental factors and one or several biological pathways consisting of sets of genes. Each biological pathway exerts its function by delivering signaling through the gene network. Theoretically, a pathway is supposed to have a robust topological structure under normal physiological conditions. However, the pathway's topological structure could be altered under some pathological condition. It is well known that a normal biological network includes a small number of well-connected hub nodes and a large number of nodes that are non-hubs...
2018: PeerJ
https://www.readbyqxmd.com/read/29659362/-recurrent-atypical-hemolytic-uremic-syndrome-after-renal-transplantation-treatment-with-eculizumab
#7
Ana B Latzke, Pehuén Fernández, Carlos Chiurchiu, Daniela Sarmantano, Javier De Arteaga, Walter Douthat, Jorge De la Fuente
Atypical hemolytic uremic syndrome (aHUS) is a rare entity. It is characterized by a thrombotic microangiopathy (nonimmune hemolytic anemia, thrombocytopenia, and acute renal failure), with a typical histopathology of thickening of capillary and arteriolar walls and an obstructive thrombosis of the vascular lumen. The syndrome is produced by a genetic or acquired deregulation of the alternative pathway of the complement system, with high rates of end stage renal disease, post-transplant recurrence, and high mortality...
2018: Medicina
https://www.readbyqxmd.com/read/29657196/atypical-hemolytic-uremic-syndrome-a-monocentric-adult-tunisian-study-and-review-of-literature
#8
R Kherder-Elfekih, M Hajji, L Ben Fatma, H Jebali, I Mami, W Smaoui, M Krid, L Rais, S Beji, K Zouaghi, M Sellami-Kallel
Atypical hemolytic uremic syndrome (aHUS) is characterized by microvascular thrombosis resulting in thrombocytopenia, hemolytic anemia, and multiorgan dysfunction. It is associated with genetic or acquired disorders of regulatory components of the complement system. For our study, we collected data from 16 patients diagnosed with aHUS between January 2010 and January 2014. The mean age was 33.6 years. The female-to-male ratio was 3. The median follow-up duration was 27 ± 3.5 months. The most common clinical presentation was hypertension...
March 2018: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/29621352/hypocomplementemia-is-associated-with-worse-renal-survival-in-anca-positive-granulomatosis-with-polyangiitis-and-microscopic-polyangiitis
#9
Samuel Deshayes, Achille Aouba, Kathy Khoy, Delphine Mariotte, Thierry Lobbedez, Nicolas Martin Silva
Recent data suggest the existence of a complement alternative pathway activation in the pathogenesis of antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV), a condition that remains poorly understood. This study aims to assess the clinical characteristics and outcomes of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) patients with regard to their plasma complement levels at diagnosis. A retrospective monocentric study carried out at Caen University Hospital led to the identification of proteinase-3- or myeloperoxidase-ANCA-positive GPA and MPA patients from January 2000 to June 2016 and from September 2011 to June 2016, respectively...
2018: PloS One
https://www.readbyqxmd.com/read/29616045/complement-factor-h-inhibits-anti-neutrophil-cytoplasmic-autoantibody-induced-neutrophil-activation-by-interacting-with-neutrophils
#10
Su-Fang Chen, Feng-Mei Wang, Zhi-Ying Li, Feng Yu, Min Chen, Ming-Hui Zhao
Our previous study demonstrated that plasma levels of complement factor H (FH) were inversely associated with the disease activity of patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). In addition to serving as an inhibitor of the alternative complement pathway, there is increasing evidence demonstrating direct regulatory roles of FH on several cell types. Here, we investigated the role of FH in the process of ANCA-mediated activation of neutrophils and neutrophil-endothelium interaction...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29616034/specific-inhibition-of-complement-activation-significantly-ameliorates-autoimmune-blistering-disease-in-mice
#11
Sidonia Mihai, Misa Hirose, Yi Wang, Joshua M Thurman, V Michael Holers, B Paul Morgan, Jörg Köhl, Detlef Zillikens, Ralf J Ludwig, Falk Nimmerjahn
Epidermolysis bullosa acquisita (EBA) is an antibody-mediated blistering skin disease associated with tissue-bound and circulating autoantibodies to type VII collagen (COL7). Transfer of antibodies against COL7 into mice results in a subepidermal blistering phenotype, strictly depending on the complement component C5. Further, activation predominantly by the alternative pathway is required to induce experimental EBA, as blistering was delayed and significantly ameliorated only in factor B-/- mice. However, C5 deficiency not only blocked the activation of terminal complement components and assembly of the membrane attack complex (MAC) but also eliminated the formation of C5a...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29615744/activation-of-the-complement-system-in-an-osteosarcoma-cell-line-promotes-angiogenesis-through-enhanced-production-of-growth-factors
#12
Hyungtaek Jeon, Seung Ro Han, Suhyuk Lee, Sang June Park, Joo Heon Kim, Seung-Min Yoo, Myung-Shin Lee
There is increasing evidence that the complement system is activated in various cancer tissues. Besides being involved in innate immunity against pathogens, the complement system also participates in inflammation and the modulation of tumor microenvironment. Recent studies suggest that complement activation promotes tumor progression in various ways. Among some cancer cell lines, we found that human bone osteosarcoma epithelial cells (U2-OS) can activate the alternative pathway of the complement system by pooled normal human serum...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29605505/comparison-of-the-susceptibility-and-resistance-of-four-marine-perciform-fishes-to-cryptocaryon-irritans-infection
#13
Fei Yin, Wenchao Liu, Peibo Bao, Shan Jin, Dong Qian, Jiteng Wang, Baojun Tang
Cryptocaryon irritans is a type of marine ectoparasitic ciliate that infects teleost fishes. To illustrate the susceptibility and innate immune mechanism of fishes to C. irritans, four species of marine perciform fishes were selected in Fujian Province, a high-prevalence area for cryptocaryoniasis in China. The survival, diameter/number of tomonts, and infection ratio among Larimichthys crocea, Lateolabrax japonicus, Pagrus major, and Nibea albiflora was compared after artificial infection. Meanwhile, the immobilization titers of four fish species with no C...
March 29, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29597356/complement-factor-d-protects-mice-from-ethanol-induced-inflammation-and-liver-injury
#14
Rebecca L McCullough, Megan R McMullen, Megan M Sheehan, Kyle L Poulsen, Sanjoy Roychowdhury, Dian J Chiang, Michele T Pritchard, Juan Caballeria, Laura E Nagy
Complement plays a crucial role in microbial defense and clearance of apoptotic cells. Emerging evidence suggests complement is an important contributor to alcoholic liver disease. While C1q-dependent complement activation contributes to ethanol-induced liver injury, the role of the alternative pathway in ethanol-induced injury is unknown. Activation of complement via the classical and alternative pathways was detected in alcoholic hepatitis patients. Female C57BL/6J (WT), C1qa-/- (lacking classical pathway activation), C4-/- (lacking classical and lectin pathway activation), FD-/- (lacking alternative pathway activation), and C1qa/FD-/- (lacking classical and alternative pathway activation) were fed an ethanol-containing liquid diet or pair-fed control diet for 4 or 25 days...
March 29, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29594148/c3-glomerulopathy-and-atypical-hemolytic-uremic-syndrome-two-important-manifestations-of-complement-system-dysfunction
#15
Ravneet Bajwa, John A DePalma, Taimoor Khan, Anmol Cheema, Sheila A Kalathil, Mohammad A Hossain, Attiya Haroon, Anne Madhurima, Min Zheng, Ali Nayer, Arif Asif
The advances in our understanding of the alternative pathway have emphasized that uncontrolled hyperactivity of this pathway causes 2 distinct disorders that adversely impact the kidney. In the so-called atypical hemolytic uremic syndrome (aHUS), renal dysfunction occurs along with thrombocytopenia, anemia, and target organ injury to multiple organs, most commonly the kidney. On the other hand, in the so-termed C3 glomerulopathy, kidney involvement is not associated with thrombocytopenia, anemia, or other system involvement...
January 2018: Case Reports in Nephrology and Dialysis
https://www.readbyqxmd.com/read/29592796/c3-glomerulopathy-in-cystic-fibrosis-a-case-report
#16
Domenico Santoro, Rossella Siligato, Carmela Vadalà, Mariacristina Lucanto, Simona Cristadoro, Giovanni Conti, Michele Buemi, Stefano Costa, Ettore Sabadini, Giuseppe Magazzù
BACKGROUND: C3 glomerulonephritis is a rare glomerulopathy characterized at renal biopsy by C3 deposition, alone or with scanty immunoglobulins, as well as by an electron-dense material in mesangium, subendothelial and subepithelial space. An abnormal systemic activation of the alternative pathway of the complement cascade is responsible for the development of the disease if triggered by several possible environmental conditions. We report the first case in literature of a patient affected by cystic fibrosis and C3GN...
March 28, 2018: BMC Nephrology
https://www.readbyqxmd.com/read/29588430/an-engineered-complement-factor-h-construct-for-treatment-of-c3-glomerulopathy
#17
Yi Yang, Harriet Denton, Owen R Davies, Kate Smith-Jackson, Heather Kerr, Andrew P Herbert, Paul N Barlow, Matthew C Pickering, Kevin J Marchbank
Background C3 glomerulopathy (C3G) is associated with dysregulation of the alternative pathway of complement activation, and treatment options for C3G remain limited. Complement factor H (FH) is a potent regulator of the alternative pathway and might offer a solution, but the mass and complexity of FH makes generation of full-length FH far from trivial. We previously generated a mini-FH construct, with FH short consensus repeats 1-5 linked to repeats 18-20 (FH1-5^18-20 ), that was effective in experimental C3G...
March 27, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29579105/neisseria-heparin-binding-antigen-is-targeted-by-the-human-alternative-pathway-c3-convertase
#18
Martina Di Fede, Massimiliano Biagini, Elena Cartocci, Carlo Parillo, Alessandra Greco, Manuele Martinelli, Sara Marchi, Alfredo Pezzicoli, Isabel Delany, Silvia Rossi Paccani
Neisserial Heparin Binding Antigen (NHBA) is a surface-exposed lipoprotein specific for Neisseria and constitutes one of the three main protein antigens of the Bexsero vaccine. Meningococcal and human proteases, cleave NHBA protein upstream or downstream of a conserved Arg-rich region, respectively. The cleavage results in the release of the C-terminal portion of the protein. The C-terminal fragment originating from the processing of meningococcal proteases, referred to as C2 fragment, exerts a toxic effect on endothelial cells altering the endothelial permeability...
2018: PloS One
https://www.readbyqxmd.com/read/29576927/encapsulated-cell-technology-based-delivery-of-a-complement-inhibitor-reduces-choroidal-neovascularization-in-a-mouse-model
#19
Balasubramaniam Annamalai, Nathaniel Parsons, Marwa Belhaj, Carlene Brandon, Jay Potts, Bärbel Rohrer
Purpose: Age-related macular degeneration (AMD) is a slowly progressing disease, and risk appears to be tied to an overactive complement system. We have previously demonstrated that mouse choroidal neovascularization (CNV) and smoke-induced ocular pathology can be reduced with an alternative pathway (AP) inhibitor fusion protein consisting of a complement receptor-2 fragment linked to the inhibitory domain of factor H (CR2-fH) when delivered systemically. Here we developed an experimental approach with genetically engineered encapsulated ARPE-19 cells to produce CR2-fH intravitreally...
March 2018: Translational Vision Science & Technology
https://www.readbyqxmd.com/read/29571059/relative-antibacterial-functions-of-complement-and-nets-nets-trap-and-complement-effectively-kills-bacteria
#20
Louiza Azzouz, Ahmed Cherry, Magdalena Riedl, Meraj Khan, Fred G Pluthero, Walter H A Kahr, Nades Palaniyar, Christoph Licht
Neutrophil extracellular traps (NETs) are web-like DNA structures released by activated neutrophils. These structures are decorated with antimicrobial proteins, and considered to trap and kill bacteria extracellularly. However, the exact functions of NETs remain elusive, and contradictory observations have been made with NETs functioning as an antimicrobial or a pathogentrapping mechanism. There is a disconnect in the interpretation of the involvement of other major immune mechanisms, such as the complement system, as effectors of the function of NETs...
March 20, 2018: Molecular Immunology
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