2023
DOI: 10.1111/bjh.18662
|View full text |Cite
|
Sign up to set email alerts
|

The long‐acting anti‐C5 ravulizumab results in C3 binding to PNH red cells similar to its parental molecule eculizumab

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1

Citation Types

1
2
0

Year Published

2023
2023
2024
2024

Publication Types

Select...
5

Relationship

1
4

Authors

Journals

citations
Cited by 5 publications
(3 citation statements)
references
References 19 publications
1
2
0
Order By: Relevance
“…4 By modeling in vitro the activation of the alternative complement pathway, it has been demonstrated that C3 binding happens when C5 is blocked either by antibodies or by different types of molecules such as coversin. 3,5,6 Altogether, these in vitro and in vivo observations confirm that C3 binding to PNH red blood cells is a phenomenon associated with the inhibition of C5. However, C3 binding has also been reported in a PNH patient that does not suffer from intravascular hemolysis because of a coexisting congenital deficiency of complement 9 (C9) 7 suggesting that it could be associated with the inhibition of any component of the terminal complement pathway.…”
supporting
confidence: 62%
See 1 more Smart Citation
“…4 By modeling in vitro the activation of the alternative complement pathway, it has been demonstrated that C3 binding happens when C5 is blocked either by antibodies or by different types of molecules such as coversin. 3,5,6 Altogether, these in vitro and in vivo observations confirm that C3 binding to PNH red blood cells is a phenomenon associated with the inhibition of C5. However, C3 binding has also been reported in a PNH patient that does not suffer from intravascular hemolysis because of a coexisting congenital deficiency of complement 9 (C9) 7 suggesting that it could be associated with the inhibition of any component of the terminal complement pathway.…”
supporting
confidence: 62%
“…Complement alternative pathway was spontaneously activated by incubation in sealed tubes with 100% atmospheric air for 24 h. However, a distinct population of PNH red blood cells bound with fragments of complement 3 (C3), specifically C3d, 3 appears in almost all PNH patients on anti-C5 therapy. 4,5 This C3d-bound population of PNH red blood cells is a potential target of the reticulo-endothelial system, with consequent variable degrees of extravascular hemolysis. 4 By modeling in vitro the activation of the alternative complement pathway, it has been demonstrated that C3 binding happens when C5 is blocked either by antibodies or by different types of molecules such as coversin.…”
mentioning
confidence: 99%
“…Subsequently, a second generation C5i, ravulizumab, also has been approved. However, a significant number of patients with PNH who receive C5is, which control IVH, become susceptible to complement component 3 (C3)–mediated extravascular hemolysis (EVH) that occurs as C3 fragments increase the opsonization of PNH red blood cells, targeting them for phagocytosis in the liver and spleen [ 14 , 15 ]. As a result, C5i-treated patients can experience chronic, low-grade hemolysis, resulting in ongoing anemia, persistent fatigue, and transfusion dependence [ 16 , 17 ].…”
Section: Introductionmentioning
confidence: 99%