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Human coagulation factor VIII (FVIII) is a key co-factor in the clotting cascade, the deficiency of which leads to Hemophilia A. Human plasma-derived (pdFVIII) and recombinant FVIII (rFVIII) had been used as effective products to prevent and treat bleeding episodes. Both FVIII products share identical amino acid sequences and appear to be equivalent as of clinical efficiency. However, systemic reviews found an increased risk of neutralizing antibody (or inhibitor) development with recombinant products. FVIII is a highly glycosylated protein, and its glycosylation pattern is specific to host cells and environments. The roles of glycosylation in immune responses toward pdFVIII and rFVIII are yet to be defined. Herein, we systemically profiled N- and O-glycomes of pdFVIII and rFVIII using a mass spectrometry-based glycoproteomic strategy. A total of 110 site-specific N-glycopeptides consisting of 61 N-glycoforms were identified quantitatively from rFVIII and pdFVIII. Additionally, 31 O-glycoforms were identified on 23 peptides from rFVIII and pdFVIII. A comprehensive comparison of their site-specific glycan profiles revealed distinct differences between the glycosylation of pdFVIII and rFVIII.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244179 | PMC |
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233576 | PLOS |
Haemophilia
May 2025
School of Medicine and Population Health, University of Sheffield, Sheffield, UK.
Background: The last 15 years have seen new extended half-life (EHL) recombinant FVIII/IX concentrates and nonreplacement therapy for haemophilia A (emicizumab) introduced in Europe. These changes affect FVIII/IX exposure in previously untreated patients (PUPs) and previously treated patients (PTPs) with severe haemophilia A and B (SHA and SHB) and may modify inhibitor development and/or detection.
Aim: To report trends in treatment for severe haemophilia and concomitant changes in inhibitor incidence.
iScience
December 2024
Chengdu Rongsheng Pharmaceuticals Co., Ltd, Chengdu 610041, China.
Hemophilia is caused by the deficiency of clotting factors due to a single genetic abnormality. Replacement therapies have evolved from plasma-derived to recombinant coagulation factor concentrates but continue to have certain limitations. Monoclonal antibodies are clinical prophylactic treatment options unaffected by inhibitors and have better compliance than coagulation factor concentrates for patients with hemophilia.
View Article and Find Full Text PDFRes Pract Thromb Haemost
November 2024
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Background: The SIPPET randomized clinical trial showed that in previously untreated patients (PUPs) with severe hemophilia A, treatment with plasma-derived factor (F)VIII (pdFVIII) within the first 50 exposure days (EDs) was associated with a lower cumulative incidence of inhibitors than with recombinant FVIII (rFVIII). Switching to rFVIII beyond 50 EDs with pdFVIII is a treatment often implemented by many centers. The question is whether or not this switch may induce a risk of inhibitor development.
View Article and Find Full Text PDFBlood Res
October 2024
CliCon S.r.l. Società Benefit, Health, Economics & Outcomes Research, Bologna, Italy.
Drugs Real World Outcomes
September 2024
Pfizer Japan Inc., Shinjuku Bunka Quint Bldg., 3-22-7, Yoyogi, Shibuya-ku, Tokyo, Japan.