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Alternative complement pathway

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https://www.readbyqxmd.com/read/28316335/complement-in-anca-associated-vasculitis-mechanisms-and-implications-for-management
#1
REVIEW
Min Chen, David R W Jayne, Ming-Hui Zhao
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of potentially life-threatening autoimmune diseases. The main histological feature in the kidneys of patients with AAV is pauci-immune necrotizing crescentic glomerulonephritis with little immunoglobulin and complement deposition in the glomerular capillary walls. The complement system was not, therefore, initially thought to be associated with the development of AAV. Accumulating evidence from animal models and clinical observations indicate, however, that activation of the complement system - and the alternative pathway in particular - is crucial for the development of AAV, and that the complement activation product C5a has a central role...
March 20, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28314229/how-did-the-good-school-toolkit-reduce-the-risk-of-past-week-physical-violence-from-teachers-to-students-qualitative-findings-on-pathways-of-change-in-schools-in-luwero-uganda
#2
N Kyegombe, S Namakula, J Mulindwa, J Lwanyaaga, D Naker, S Namy, J Nakuti, J Parkes, L Knight, E Walakira, K M Devries
Violence against children is a serious violation of children's rights with significant impacts on current and future health and well-being. The Good School Toolkit (GST) is designed to prevent violence against children in primary schools through changing schools' operational cultures. Conducted in the Luwero District in Uganda between 2012 and 2014, findings from previous research indicate that the Toolkit reduced the odds of past week physical violence from school staff (OR = 0.40, 95%CI 0.26-0.64, p < 0...
March 7, 2017: Social Science & Medicine
https://www.readbyqxmd.com/read/28303635/incident-microalbuminuria-and-complement-factor-mannan-binding-lectin-associated-protein-19-in-people-with-newly-diagnosed-type-1-diabetes
#3
J A Ostergaard, S Thiel, I T Hoffmann-Petersen, P Hovind, H-H Parving, L Tarnow, P Rossing, T K Hansen
BACKGROUND: Evidence links the lectin pathway of complement activation to diabetic kidney disease. Upon carbohydrate-recognition by pattern-recognition molecules, e.g., mannan-binding lectin (MBL), the MBL-associated serine protease (MASP-2) is activated and initiates the complement cascade. The MASP2 gene encodes MASP-2 and the alternative splice product MBL-associated protein 19 (MAp19). Both MAp19 and MASP-2 circulate in complex with MBL. We tested the hypothesis that MAp19 and MASP-2 concentrations predict the risk of incident microalbuminuria...
March 16, 2017: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/28301559/synergy-between-the-classical-and-alternative-pathways-of-complement-is-essential-for-conferring-effective-protection-against-the-pandemic-influenza-a-h1n1-2009-virus-infection
#4
Ajitanuj Rattan, Shailesh D Pawar, Renuka Nawadkar, Neeraja Kulkarni, Girdhari Lal, Jayati Mullick, Arvind Sahu
The pandemic influenza A(H1N1) 2009 virus caused significant morbidity and mortality worldwide thus necessitating the need to understand the host factors that influence its control. Previously, the complement system has been shown to provide protection during the seasonal influenza virus infection, however, the role of individual complement pathways is not yet clear. Here, we have dissected the role of intact complement as well as of its individual activation pathways during the pandemic influenza virus infection using mouse strains deficient in various complement components...
March 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28293529/facial-nerve-recovery-in-kbdb-and-c1q-knockout-mice-a-role-for-histocompatibility-complex-1
#5
Seden Akdagli, Ryan A Williams, Hyun J Kim, Yuling Yan, Mirna Mustapha, Sam P Most
BACKGROUND: Understanding the mechanisms in nerve damage can lead to better outcomes for neuronal rehabilitation. The purpose of our study was to assess the effect of major histocompatibility complex I deficiency and inhibition of the classical complement pathway (C1q) on functional recovery and cell survival in the facial motor nucleus (FMN) after crush injury in adult and juvenile mice. METHODS: A prospective blinded analysis of functional recovery and cell survival in the FMN after a unilateral facial nerve crush injury in juvenile and adult mice was undertaken between wild-type, C1q knockout (C1q-/-), and KbDb knockout (KbDb-/-) groups...
December 2016: Plastic and Reconstructive Surgery. Global Open
https://www.readbyqxmd.com/read/28287636/transplant-associated-thrombotic-microangiopathy-opening-pandora-s-box
#6
REVIEW
E Gavriilaki, I Sakellari, A Anagnostopoulos, R A Brodsky
Transplant-associated thrombotic microangiopathy (TA-TMA) is an early complication of hematopoietic cell transplantation (HCT). A high mortality rate is documented in patients who are refractory to calcineurin inhibitor cessation. Estimates of TA-TMA prevalence vary significantly and are higher in allogeneic compared with autologous HCT. Furthermore, our understanding of the pathophysiology that is strongly related to diagnosis and treatment options is limited. Recent evidence has linked TA-TMA with atypical hemolytic uremic syndrome, a disease of excessive activation of the alternative pathway of complement, opening the Pandora's box in treatment options...
March 13, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28287003/non-specific-adsorption-of-complement-proteins-affects-complement-activation-pathways-of-gold-nanomaterials
#7
Quang Huy Quach, James Chen Yong Kah
The complement system is a key humoral component of innate immunity, serving as the first line of defense against intruders, including foreign synthetic nanomaterials. Although gold nanomaterials (AuNMs) are widely used in nanomedicine, their immunological response is not well understood. Using AuNMs of three shapes commonly used in biomedical applications: spherical gold nanoparticles, gold nanostars and gold nanorods, we demonstrated that AuNMs activated whole complement system, leading to the formation of SC5b-9 complex...
March 11, 2017: Nanotoxicology
https://www.readbyqxmd.com/read/28278252/complement-inhibition-by-sarcoptes-scabiei-protects-streptococcus-pyogenes-an-in-vitro-study-to-unravel-the-molecular-mechanisms-behind-the-poorly-understood-predilection-of-s-pyogenes-to-infect-mite-induced-skin-lesions
#8
Pearl M Swe, Lindsay D Christian, Hieng C Lu, Kadaba S Sriprakash, Katja Fischer
BACKGROUND: On a global scale scabies is one of the most common dermatological conditions, imposing a considerable economic burden on individuals, communities and health systems. There is substantial epidemiological evidence that in tropical regions scabies is often causing pyoderma and subsequently serious illness due to invasion by opportunistic bacteria. The health burden due to complicated scabies causing cellulitis, bacteraemia and sepsis, heart and kidney diseases in resource-poor communities is extreme...
March 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28277777/riemerella-anatipestifer-extracellular-protease-s-blocks-complement-activation-via-the-classical-and-lectin-pathways
#9
Mengnan Fan, Sihuai Chen, Ludan Zhang, Junxuan Bi, Jiasun Peng, Xinyan Huang, Xin Li, Huan Li, Qin Zhou, Sheng Jiang, Jixiang Li
Riemerella anatipestifer (RA) is the causative agent of infectious serositis in ducklings and other avian species. It is difficult to control the disease due to its 21 serotypes, poor cross-protection, and bacterial resistance to antimicrobial agents. The complement system is an important component of the innate immune system. However, bacterial pathogens exploit several strategies to evade detection by the complement system. Here, we purified and identified a 59-kDa RA extracellular protease S (EcpS) consisting of a gelatinase...
March 2, 2017: Avian Pathology: Journal of the W.V.P.A
https://www.readbyqxmd.com/read/28276660/complement-alternative-pathway-deficiency-in-recipients-protects-kidney-allograft-from-ischemia-reperfusion-injury-and-alloreactive-t-cell-response
#10
Federica Casiraghi, Nadia Azzollini, Marta Todeschini, Sonia Fiori, Regiane Aparecida Cavinato, Paola Cassis, Samantha Solini, Francesca Pezzuto, Marilena Mister, Joshua M Thurman, Ariela Benigni, Giuseppe Remuzzi, Marina Noris
Despite the introduction of novel and more targeted immunosuppressive drugs, the long-term survival of kidney transplants has not improved satisfactorily. Early antigen-independent intra-graft inflammation plays a critical role in the initiation of the alloimmune response and impacts long-term graft function. Complement activation is a key player both in ischemia/reperfusion injury (IRI) as well as in adaptive anti-graft immune response after kidney transplantation. Since the alternative pathway (AP) amplifies complement activation regardless of the initiation pathways and renal IR injured cells undergo uncontrolled complement activation, we wondered whether selective blockade of AP could be a strategy for prolonging kidney graft survival...
March 9, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28264884/functional-and-structural-insight-into-properdin-control-of-complement-alternative-pathway-amplification
#11
Dennis V Pedersen, Lubka Roumenina, Rasmus K Jensen, Trine Af Gadeberg, Chiara Marinozzi, Capucine Picard, Tania Rybkine, Steffen Thiel, Uffe Bs Sørensen, Cordula Stover, Veronique Fremeaux-Bacchi, Gregers R Andersen
Properdin (FP) is an essential positive regulator of the complement alternative pathway (AP) providing stabilization of the C3 and C5 convertases, but its oligomeric nature challenges structural analysis. We describe here a novel FP deficiency (E244K) caused by a single point mutation which results in a very low level of AP activity. Recombinant FP E244K is monomeric, fails to support bacteriolysis, and binds weakly to C3 products. We compare this to a monomeric unit excised from oligomeric FP, which is also dysfunctional in bacteriolysis but binds the AP proconvertase, C3 convertase, C3 products and partially stabilizes the convertase...
March 6, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28262211/complement-alternative-pathway-s-activation-in-patients-with-lupus-nephritis
#12
Di Song, Wei-Yi Guo, Feng-Mei Wang, Yong-Zhe Li, Yan Song, Feng Yu, Ming-Hui Zhao
OBJECTIVE: The aim of this study was to detect the spectrum of complement activation pathways in circulation and to assess their correlations with clinical and pathologic features in a large lupus nephritis cohort from China. MATERIALS AND METHODS: Plasma levels of C1q, mannose-binding lectin, C4d, Bb, C3, C3a, C5a and soluble C5b-9 were detected by enzyme-linked immunosorbent assay in 222 patients with active biopsy-proven lupus nephritis, 34 patients with lupus nephritis at remission, 82 patients with active systemic lupus erythematosus without renal involvement and 39 normal controls...
March 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28258151/staphylococcus-aureussdre-captures-the-factor-h-c-terminus-via-a-novel-close-dock-lock-and-latch-mechanism-for-complement-evasion
#13
Yingjie Zhang, Minhao Wu, Tianrong Hang, Chengliang Wang, Ye Yang, Weimin Pan, Jianye Zang, Min Zhang, Xuan Zhang
Complement factor H (CFH) is a soluble complement regulatory protein essential for the downregulation of the alternative pathway upon interaction with specific markers on host cell surface. It recognizes the complement component 3b (C3b) and 3d (C3d) fragments in addition to self cell markers (i.e. glycosaminoglycans (GAG), sialic acid) to distinguish host cells that deserve protection from pathogens that need elimination. The Staphylococcus aureus surface protein serine-aspartate repeat protein E (SdrE) was previously reported to bind human CFH as an immune-evasion tactic...
March 3, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28254726/ionic-tethering-contributes-to-the-conformational-stability-and-function-of-complement-c3b
#14
Andrés López-Perrote, Reed E S Harrison, Marta Subías, Martín Alcorlo, Santiago Rodríguez de Córdoba, Dimitrios Morikis, Oscar Llorca
C3b, the central component of the alternative pathway (AP) of the complement system, coexists as a mixture of conformations in solution. These conformational changes can affect interactions with other proteins and complement regulators. Here we combine a computational model for electrostatic interactions within C3b with molecular imaging to study the conformation of C3b. The computational analysis shows that the TED domain in C3b is tethered ionically to the macroglobulin (MG) ring. Monovalent counterion concentration affects the magnitude of electrostatic forces anchoring the TED domain to the rest of the C3b molecule in a thermodynamic model...
February 27, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28250608/complements-spurned-our-experience-with-atypical-hemolytic-uremic-syndrome
#15
Vidya S Nagar, Rudrarpan Chaterjee, Ankita Sood, Basavaraj Sajjan, Aniruddha Kaushik, Sameer V Vyahalkar
Atypical hemolytic uremic syndrome (aHUS) is a rare disorder resulting from a dysregulated activation of the alternative pathway of the complement system. It results in significant morbidity and mortality if not diagnosed and treated promptly. It lends itself to myriad renal and extrarenal manifestations, all potentially disabling. Eculizumab, a monoclonal antibody to complement C5 is now the widely accepted norm for treatment. However, in resource-limited settings, plasma exchange if instituted early may be as beneficial...
February 2017: Indian Journal of Critical Care Medicine
https://www.readbyqxmd.com/read/28248200/the-role-of-the-complement-system-in-cancer
#16
REVIEW
Vahid Afshar-Kharghan
In addition to being a component of innate immunity and an ancient defense mechanism against invading pathogens, complement activation also participates in the adaptive immune response, inflammation, hemostasis, embryogenesis, and organ repair and development. Activation of the complement system via classical, lectin, or alternative pathways generates anaphylatoxins (C3a and C5a) and membrane attack complex (C5b-9) and opsonizes targeted cells. Complement activation end products and their receptors mediate cell-cell interactions that regulate several biological functions in the extravascular tissue...
March 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28236143/c3-glomerulopathy-and-eculizumab-a-report-on-four-paediatric-cases
#17
Célia Lebreton, Justine Bacchetta, Frédérique Dijoud, Lucie Bessenay, Véronique Fremeaux-Bacchi, Anne Laure Sellier-Leclerc
BACKGROUND: Eculizumab may be used to treat C3-glomerulopathy (C3G), a rare but severe glomerular disease. DIAGNOSIS AND TREATMENT: Patients 1, 2 and 3 were diagnosed with nephritic syndrome with alternative complement pathway activation (low C3, C3Nef-positive) and C3G at the age of 9, 13 and 12 years, respectively. Treatment with eculizumab normalized proteinuria within 1, 2 and 7 months, respectively. Proteinuria relapsed when eculizumab was withdrawn, but the re-introduction of eculizumab normalized proteinuria...
February 24, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28210841/rare-genetic-variant-in-the-cfb-gene-presenting-as-atypical-hemolytic-uremic-syndrome-and-immune-complex-diffuse-membranoproliferative-glomerulonephritis-with-crescents-successfully-treated-with-eculizumab
#18
Khalid Alfakeeh, Mohammed Azar, Majid Alfadhel, Alsuayri Mansour Abdullah, Nourah Aloudah, Khaled O Alsaad
BACKGROUND: Complement factor B gene (CFB) is an important component of the alternate pathway of complement activation that provides an active subunit that associates with C3b to form the C3 convertase, which is an essential element in complement activation. Among the complement-associated disorders, mutations and pathogenic variants in the CFB gene are relatively rare phenomena. Moreover, mutated CFB affiliation with immune-complex diffuse membranoproliferative glomerulonephritis (IC-MPGN) and atypical hemolytic uremic syndrome (aHUS) are considered a highly rare occurrence...
February 16, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28195242/the-alternative-complement-pathway-is-dysregulated-in-patients-with-chronic-heart-failure
#19
Negar Shahini, Annika E Michelsen, Per H Nilsson, Karin Ekholt, Lars Gullestad, Kaspar Broch, Christen P Dahl, Pål Aukrust, Thor Ueland, Tom Eirik Mollnes, Arne Yndestad, Mieke C Louwe
The complement system, an important arm of the innate immune system, is activated in heart failure (HF). We hypothesized that HF patients are characterized by an imbalance of alternative amplification loop components; including properdin and complement factor D and the alternative pathway inhibitor factor H. These components and the activation product, terminal complement complex (TCC), were measured in plasma from 188 HF patients and 67 age- and sex- matched healthy controls by enzyme immunoassay. Our main findings were: (i) Compared to controls, patients with HF had significantly increased levels of factor D and TCC, and decreased levels of properdin, particularly patients with advanced clinical disorder (i...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28191609/complement-blockade-in-anca-associated-vasculitis-an-index-case-current-concepts-and-future-perspectives
#20
REVIEW
Lucio Manenti, Maria Letizia Urban, Federica Maritati, Maricla Galetti, Augusto Vaglio
Complement alternative pathway (cAP) hyperactivation seems to be involved in ANCA-associated vasculitis (AAV). We here describe a case of AAV with severe activation of cAP that developed acute renal failure. No mutation predisposing to cAP dysregulation was identified. We treated our patient with the standard immunosuppressive therapy, but disease progression was only reversed after the addition of eculizumab, a monoclonal antibody against C5; the patient eventually achieved an almost complete renal function recovery...
February 13, 2017: Internal and Emergency Medicine
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