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Qualification of Hemophilia Treatment Centers to Enable Multi-Center Studies of Gene Expression Signatures in Blood Cells from Pediatric Patients

Hemophilia A is a rare congenital bleeding disorder caused by a deficiency of functionally active coagulation factor VIII (FVIII). Most patients with the severe form of the disease require FVIII replacement therapies, which are often associated with the development of neutralizing antibodies against...

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Autores principales: Reipert, Birgit M., Hofbauer, Christoph J., Gangadharan, Bagirath, Berg, Verena, Donnachie, Elizabeth, Meeks, Shannon, Mancuso, Maria Elisa, Bowen, Joel, Brown, Deborah L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10004246/
https://www.ncbi.nlm.nih.gov/pubmed/36902866
http://dx.doi.org/10.3390/jcm12052080
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author Reipert, Birgit M.
Hofbauer, Christoph J.
Gangadharan, Bagirath
Berg, Verena
Donnachie, Elizabeth
Meeks, Shannon
Mancuso, Maria Elisa
Bowen, Joel
Brown, Deborah L.
author_facet Reipert, Birgit M.
Hofbauer, Christoph J.
Gangadharan, Bagirath
Berg, Verena
Donnachie, Elizabeth
Meeks, Shannon
Mancuso, Maria Elisa
Bowen, Joel
Brown, Deborah L.
author_sort Reipert, Birgit M.
collection PubMed
description Hemophilia A is a rare congenital bleeding disorder caused by a deficiency of functionally active coagulation factor VIII (FVIII). Most patients with the severe form of the disease require FVIII replacement therapies, which are often associated with the development of neutralizing antibodies against FVIII. Why some patients develop neutralizing antibodies while others do not is not fully understood. Previously, we could demonstrate that the analysis of FVIII-induced gene expression signatures in peripheral blood mononuclear cells (PBMC) obtained from patients exposed to FVIII replacement therapies provides novel insights into underlying immune mechanisms regulating the development of different populations of FVIII-specific antibodies. The aim of the study described in this manuscript was the development of training and qualification test procedures to enable local operators in different European and US clinical Hemophilia Treatment Centers (HTC) to produce reliable and valid data for antigen-induced gene expression signatures in PBMC obtained from small blood volumes. For this purpose, we used the model antigen Cytomegalovirus (CMV) phosphoprotein (pp) 65. We trained and qualified 39 local HTC operators from 15 clinical sites in Europe and the US, of whom 31 operators passed the qualification at first attempt, and eight operators passed at the second attempt.
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spelling pubmed-100042462023-03-11 Qualification of Hemophilia Treatment Centers to Enable Multi-Center Studies of Gene Expression Signatures in Blood Cells from Pediatric Patients Reipert, Birgit M. Hofbauer, Christoph J. Gangadharan, Bagirath Berg, Verena Donnachie, Elizabeth Meeks, Shannon Mancuso, Maria Elisa Bowen, Joel Brown, Deborah L. J Clin Med Article Hemophilia A is a rare congenital bleeding disorder caused by a deficiency of functionally active coagulation factor VIII (FVIII). Most patients with the severe form of the disease require FVIII replacement therapies, which are often associated with the development of neutralizing antibodies against FVIII. Why some patients develop neutralizing antibodies while others do not is not fully understood. Previously, we could demonstrate that the analysis of FVIII-induced gene expression signatures in peripheral blood mononuclear cells (PBMC) obtained from patients exposed to FVIII replacement therapies provides novel insights into underlying immune mechanisms regulating the development of different populations of FVIII-specific antibodies. The aim of the study described in this manuscript was the development of training and qualification test procedures to enable local operators in different European and US clinical Hemophilia Treatment Centers (HTC) to produce reliable and valid data for antigen-induced gene expression signatures in PBMC obtained from small blood volumes. For this purpose, we used the model antigen Cytomegalovirus (CMV) phosphoprotein (pp) 65. We trained and qualified 39 local HTC operators from 15 clinical sites in Europe and the US, of whom 31 operators passed the qualification at first attempt, and eight operators passed at the second attempt. MDPI 2023-03-06 /pmc/articles/PMC10004246/ /pubmed/36902866 http://dx.doi.org/10.3390/jcm12052080 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Reipert, Birgit M.
Hofbauer, Christoph J.
Gangadharan, Bagirath
Berg, Verena
Donnachie, Elizabeth
Meeks, Shannon
Mancuso, Maria Elisa
Bowen, Joel
Brown, Deborah L.
Qualification of Hemophilia Treatment Centers to Enable Multi-Center Studies of Gene Expression Signatures in Blood Cells from Pediatric Patients
title Qualification of Hemophilia Treatment Centers to Enable Multi-Center Studies of Gene Expression Signatures in Blood Cells from Pediatric Patients
title_full Qualification of Hemophilia Treatment Centers to Enable Multi-Center Studies of Gene Expression Signatures in Blood Cells from Pediatric Patients
title_fullStr Qualification of Hemophilia Treatment Centers to Enable Multi-Center Studies of Gene Expression Signatures in Blood Cells from Pediatric Patients
title_full_unstemmed Qualification of Hemophilia Treatment Centers to Enable Multi-Center Studies of Gene Expression Signatures in Blood Cells from Pediatric Patients
title_short Qualification of Hemophilia Treatment Centers to Enable Multi-Center Studies of Gene Expression Signatures in Blood Cells from Pediatric Patients
title_sort qualification of hemophilia treatment centers to enable multi-center studies of gene expression signatures in blood cells from pediatric patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10004246/
https://www.ncbi.nlm.nih.gov/pubmed/36902866
http://dx.doi.org/10.3390/jcm12052080
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