Development of Complement Inhibitors to Limit Tissue as Adjuvants to Resuscitation

2010 ◽  
Author(s):  
Yuang-Taung Juang
Keyword(s):  
Complement Inhibitors

scholarly journals Halting targeted and collateral damage to red blood cells by the complement system

2021 ◽  
Author(s):  
M. Jalink ◽  
E. C. W. de Boer ◽  
D. Evers ◽  
M. Q. Havinga ◽  
J. M. I. Vos ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Complement System ◽  
Blood Cells ◽  
Defense Mechanism ◽  
Standard Of Care ◽  
Complement Protein ◽  
Complement Inhibition ◽  
Complement Inhibitors ◽  
The Complement System ◽  
Patient Burden

AbstractThe complement system is an important defense mechanism against pathogens; however, in certain pathologies, the system also attacks human cells, such as red blood cells (RBCs). In paroxysmal nocturnal hemoglobinuria (PNH), RBCs lack certain complement regulators which sensitize them to complement-mediated lysis, while in autoimmune hemolytic anemia (AIHA), antibodies against RBCs may initiate complement-mediated hemolysis. In recent years, complement inhibition has improved treatment prospects for these patients, with eculizumab now the standard of care for PNH patients. Current complement inhibitors are however not sufficient for all patients, and they come with high costs, patient burden, and increased infection risk. This review gives an overview of the underlying pathophysiology of complement-mediated hemolysis in PNH and AIHA, the role of therapeutic complement inhibition nowadays, and the high number of complement inhibitors currently under investigation, as for almost every complement protein, an inhibitor is being developed. The focus lies with novel therapeutics that inhibit complement activity specifically in the pathway that causes pathology or those that reduce costs or patient burden through novel administration routes.

scholarly journals Proteomic Characterization of Bacteriophage Peptides from the Mastitis Producer Staphylococcus aureus by LC-ESI-MS/MS and the Bacteriophage Phylogenomic Analysis

Foods ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 799
Author(s):  
Ana G. Abril ◽  
Mónica Carrera ◽  
Karola Böhme ◽  
Jorge Barros-Velázquez ◽  
Benito Cañas ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Dairy Products ◽  
Phylogenomic Analysis ◽  
Esi Ms ◽  
Complement Inhibitors ◽  
Staphylococcus Spp ◽  
The Relationship ◽  
Phage Proteins ◽  
Identification And Characterization

The present work describes LC-ESI-MS/MS MS (liquid chromatography-electrospray ionization-tandem mass spectrometry) analyses of tryptic digestion peptides from phages that infect mastitis-causing Staphylococcus aureus isolated from dairy products. A total of 1933 nonredundant peptides belonging to 1282 proteins were identified and analyzed. Among them, 79 staphylococcal peptides from phages were confirmed. These peptides belong to proteins such as phage repressors, structural phage proteins, uncharacterized phage proteins and complement inhibitors. Moreover, eighteen of the phage origin peptides found were specific to S. aureus strains. These diagnostic peptides could be useful for the identification and characterization of S. aureus strains that cause mastitis. Furthermore, a study of bacteriophage phylogeny and the relationship among the identified phage peptides and the bacteria they infect was also performed. The results show the specific peptides that are present in closely related phages and the existing links between bacteriophage phylogeny and the respective Staphylococcus spp. infected.

The Future Use of Complement Inhibitors for the Treatment of Neurological Diseases

Drugs ◽  
1998 ◽  
Vol 55 (6) ◽  
pp. 739-746 ◽  
Author(s):  
Edith G. McGeer ◽  
Patrick L. McGeer
Keyword(s):  
Neurological Diseases ◽  
Complement Inhibitors ◽  
The Future

scholarly journals Salivary complement inhibitors from mosquitoes: Structure and mechanism of action

2020 ◽  
pp. jbc.RA120.015230
Author(s):  
Ethan C Strayer ◽  
Stephen Lu ◽  
Jose M. Ribeiro ◽  
John F. Andersen
Keyword(s):  
Functional Role ◽  
Alternative Pathway ◽  
Malaria Vectors ◽  
Salivary Proteins ◽  
Plasma Extravasation ◽  
Lower Affinity ◽  
Anopheles Mosquitoes ◽  
Highly Active ◽  
Complement Inhibitors ◽  
Insight Into

Inhibition of the alternative pathway (AP) of complement by saliva from Anopheles mosquitoes facilitates feeding by blocking production of the anaphylatoxins C3a and C5a which activate mast cells leading to plasma extravasation, pain and itching. We have previously shown that albicin, a member of the SG7 protein family from An. albimanus blocks the AP by binding to and inhibiting the function of the C3 convertase, C3bBb. Here we show that SG7.AF, the albicin homolog from An. freeborni, has a similar potency to albicin but is more active in the presence of properdin, a plasma protein that acts to stabilize C3bBb. Conversely, albicin is highly active in the absence or presence of properdin. Albicin and SG7.AF stabilize the C3bBb complex in a form that accumulates on surface plasmon resonance (SPR) surfaces coated with properdin but SG7.AF binds with lower affinity than albicin. Albicin induces oligomerization of the complex in solution, suggesting that it is oligomerization that leads to stabilization on SPR surfaces. Anophensin, the albicin ortholog from An. stephensi, is only weakly active as an inhibitor of the AP, suggesting that the SG7 family may play a different functional role in this species and other species of the subgenus Cellia, containing the major malaria vectors in Africa and Asia. Crystal structures of albicin and SG7.AF reveal a novel four-helix bundle arrangement, that is stabilized by a N-terminal hydrogen bonding network. These structures provide insight into the SG7 family and related mosquito salivary proteins including the platelet-inhibitory 30kDa family.

Role of complement and the use of complement Inhibitors in the Acute DSS Model of IBD

2009 ◽  
Vol 15 ◽  
pp. S31
Author(s):  
J Schepp ◽  
C Atkinson ◽  
F Qiao ◽  
J Spearman ◽  
G Gilkeson ◽  
...  
Keyword(s):  
Complement Inhibitors

Scabies mite complement inhibitors promote growth of Group A Streptococcus

2011 ◽  
Vol 48 (14) ◽  
pp. 1697
Author(s):  
K.F. Fischer ◽  
A. Mika ◽  
D.A. Pickering ◽  
S. Reynolds ◽  
D. McMillan ◽  
...  
Keyword(s):  
Group A Streptococcus ◽  
Complement Inhibitors ◽  
Scabies Mite ◽  
Group A

Advancing therapeutic complement inhibition in hematologic diseases: PNH and beyond

Blood ◽  
2021 ◽  
Author(s):  
Eleni Gavriilaki ◽  
Régis Peffault de Latour ◽  
Antonio Maria Risitano
Keyword(s):  
Complement Activation ◽  
Lectin Pathway ◽  
Prototype Model ◽  
Complement Inhibition ◽  
Hematologic Diseases ◽  
Classical Complement Pathway ◽  
Complement Inhibitors ◽  
Hemolytic Transfusion Reaction ◽  
Personalized Approach ◽  
Long Acting

Complement is an elaborate system of the innate immunity. Genetic variants and autoantibodies leading to excessive complement activation are implicated in a variety of human diseases. Among them, the hematologic disease paroxysmal nocturnal hemoglobinuria (PNH) remains the prototype model of complement activation and inhibition. Eculizumab, the first-in-class complement inhibitor, was approved for PNH in 2007. Addressing some of the unmet needs, a long-acting C5 inhibitor, ravulizumab, and a C3 inhibitor, pegcetacoplan have been also now approved with PNH. Novel agents, such as factor B and factor D inhibitors, are under study with very promising results. In this era of several approved targeted complement therapeutics, selection of the proper drug needs to be based on a personalized approach. Beyond PNH, complement inhibition has also shown efficacy and safety in cold agglutinin disease (CAD), primarily with the C1s inhibitor of the classical complement pathway, sutimlimab, but also with pegcetacoplan. Furthermore, C5 inhibition with eculizumab and ravulizumab, as well as inhibition of the lectin pathway with narsoplimab, are investigated in transplant-associated thrombotic microangiopathy (TA-TMA). With this revolution of next-generation complement therapeutics, additional hematologic entities, such as delayed hemolytic transfusion reaction (DHTR) or immune thrombocytopenia (ITP), might also benefit from complement inhibitors. Therefore, this review aims to describe state-of-the-art knowledge of targeting complement in hematologic diseases focusing on: a) complement biology for the clinician, b) complement activation and therapeutic inhibition in prototypical complement-mediated hematologic diseases, c) hematologic entities under investigation for complement inhibition, and d) other complement-related disorders of potential interest to hematologists.

Complement Inhibitors Targeting C3, C4, and C5

2003 ◽  
pp. 75-112 ◽  
Author(s):  
Arvind Sahu ◽  
Dimitrios Morikis ◽  
John D. Lambris
Keyword(s):  
Complement Inhibitors
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