scholarly journals Effects of complement inhibition on the ABC phenomenon in rats

2017 ◽  
Vol 12 (3) ◽  
pp. 250-258 ◽  
Author(s):  
Lirong Wang ◽  
Yuqing Su ◽  
Xuling Wang ◽  
Kaifan Liang ◽  
Mengyang Liu ◽  
...  
Keyword(s):  
Complement Inhibition ◽  
Abc Phenomenon

scholarly journals A Review of Completed and Ongoing Complement Inhibitor Trials for Geographic Atrophy Secondary to Age-Related Macular Degeneration

2021 ◽  
Vol 10 (12) ◽  
pp. 2580
Author(s):  
Omar A. Halawa ◽  
Jonathan B. Lin ◽  
Joan W. Miller ◽  
Demetrios G. Vavvas
Keyword(s):  
Macular Degeneration ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Western World ◽  
Complement Factor ◽  
Complement Protein ◽  
Pivotal Phase ◽  
Complement Inhibition ◽  
Exudative Amd ◽  
Age Related

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness among older adults in the Western world. While therapies exist for patients with exudative AMD, there are currently no approved therapies for non-exudative AMD and its advanced form of geographic atrophy (GA). The discovery of genetic variants in complement protein loci with increased susceptibility to AMD has led to the investigation of the role of complement inhibition in AMD with a focus on GA. Here, we review completed and ongoing clinical trials evaluating the safety and efficacy of these studies. Overall, complement inhibition in GA has yielded mixed results. The inhibition of complement factor D has failed pivotal phase 3 trials. Studies of C3 and C5 inhibition meeting their primary endpoint are limited by high rates of discontinuation and withdrawal in the treatment arm and higher risks of conversion to exudative AMD. Studies evaluating other complement members (CFB, CFH, CFI and inhibitors of membrane attack complex—CD59) are ongoing and could offer other viable strategies.

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 Chronic complement dysregulation drives neuroinflammation after traumatic brain injury: a transcriptomic study

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Amer Toutonji ◽  
Mamatha Mandava ◽  
Silvia Guglietta ◽  
Stephen Tomlinson
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Complement System ◽  
Classical Pathway ◽  
Post Injury ◽  
Complement Inhibition ◽  
Time Points ◽  
Complement Gene ◽  
The Complement System

AbstractActivation of the complement system propagates neuroinflammation and brain damage early and chronically after traumatic brain injury (TBI). The complement system is complex and comprises more than 50 components, many of which remain to be characterized in the normal and injured brain. Moreover, complement therapeutic studies have focused on a limited number of histopathological outcomes, which while informative, do not assess the effect of complement inhibition on neuroprotection and inflammation in a comprehensive manner. Using high throughput gene expression technology (NanoString), we simultaneously analyzed complement gene expression profiles with other neuroinflammatory pathway genes at different time points after TBI. We additionally assessed the effects of complement inhibition on neuropathological processes. Analyses of neuroinflammatory genes were performed at days 3, 7, and 28 post injury in male C57BL/6 mice following a controlled cortical impact injury. We also characterized the expression of 59 complement genes at similar time points, and also at 1- and 2-years post injury. Overall, TBI upregulated the expression of markers of astrogliosis, immune cell activation, and cellular stress, and downregulated the expression of neuronal and synaptic markers from day 3 through 28 post injury. Moreover, TBI upregulated gene expression across most complement activation and effector pathways, with an early emphasis on classical pathway genes and with continued upregulation of C2, C3 and C4 expression 2 years post injury. Treatment using the targeted complement inhibitor, CR2-Crry, significantly ameliorated TBI-induced transcriptomic changes at all time points. Nevertheless, some immune and synaptic genes remained dysregulated with CR2-Crry treatment, suggesting adjuvant anti-inflammatory and neurotropic therapy may confer additional neuroprotection. In addition to characterizing complement gene expression in the normal and aging brain, our results demonstrate broad and chronic dysregulation of the complement system after TBI, and strengthen the view that the complement system is an attractive target for TBI therapy.

Gemcitabine-Associated Thrombotic Microangiopathy: Response to Complement Inhibition and Reinitiation of Gemcitabine

2017 ◽  
Vol 16 (2) ◽  
pp. e119-e122 ◽  
Author(s):  
Jeffrey L. Turner ◽  
Joshua Reardon ◽  
Tanios Bekaii-Saab ◽  
Spero R. Cataland ◽  
Matthew J. Arango
Keyword(s):  
Thrombotic Microangiopathy ◽  
Complement Inhibition

T cell-independent B cell response is responsible for ABC phenomenon induced by repeated injection of PEGylated liposomes

2010 ◽  
Vol 392 (1-2) ◽  
pp. 218-223 ◽  
Author(s):  
Hiroyuki Koide ◽  
Tomohiro Asai ◽  
Kentaro Hatanaka ◽  
Shuji Akai ◽  
Takayuki Ishii ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Response ◽  
Repeated Injection ◽  
Pegylated Liposomes ◽  
Abc Phenomenon ◽  
B Cell Response

Complement inhibition rescued mice allowing observation of transgene expression following intraportal delivery of baculovirus in mice

2005 ◽  
Vol 7 (3) ◽  
pp. 325-333 ◽  
Author(s):  
Jonathan Hoare ◽  
Simon Waddington ◽  
Howard C. Thomas ◽  
Charles Coutelle ◽  
Michael J. McGarvey
Keyword(s):  
Transgene Expression ◽  
Complement Inhibition

Ovarian Cancer Ascites Induces a Suppressor Phenotype in Monocytes that is Abrogated with Complement Inhibition

2020 ◽  
Vol 158 (1) ◽  
pp. e4-e5
Author(s):  
J. Ricciuti ◽  
T. Emmons ◽  
A.N.H. Khan ◽  
T. Giridharan ◽  
E. Zsiros ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Complement Inhibition

scholarly journals Adult post COVID-19 multisystem inflammatory syndrome and thrombotic microangiopathy

2020 ◽  
Author(s):  
Idris Boudhabhay ◽  
Marion Rabant ◽  
Louis-Marie Coupry ◽  
Armance Marchal ◽  
Lubka T Roumenina ◽  
...  
Keyword(s):  
Renal Function ◽  
Thrombotic Microangiopathy ◽  
Dramatic Improvement ◽  
Case Presentation ◽  
Complement Inhibition ◽  
Clinical Series ◽  
Long Term Consequences ◽  
Inflammatory Syndrome

Abstract Background: The coronavirus disease 2019 pandemic has affected millions of people worldwide but medium and long-term consequences are unknown. Clinical series of Kawasaki-like multisystem inflammatory syndrome in children (MIS-C), occurring after SARS-Cov-2 spreading, have been recently described. Case presentation: We describe a case of post COVID-19 MIS in a 46-year-old man, with biopsy-proven renal thrombotic microangiopathy (TMA). Specific complement inhibition with Eculizumab was initiated promptly and lead to a dramatic improvement of renal function. Conclusion: Our case suggests that post COVID-19 MIS is not restricted to children and that TMA could play a central role in the pathophysiology of this syndrome

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