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A FCGR3A Polymorphism Predicts Anti-drug Antibodies in Chronic Inflammatory Bowel Disease Patients Treated With Anti-TNF

Background. The production of anti-drug antibodies (ADAs) against IgG monoclonal antibodies (mAbs) targeting tumour necrosis factor (TNF) is an important cause of loss of response to anti-TNF mAbs in patients with inflammatory bowel diseases (IBD) such as Crohn's disease (CD) and ulcerative col...

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Autores principales: Romero-Cara, Patricia, Torres-Moreno, Daniel, Pedregosa, José, Vílchez, Juan Antonio, García-Simón, María Sergia, Ruiz-Merino, Guadalupe, Morán-Sanchez, Senador, Conesa-Zamora, Pablo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2018
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765734/
https://www.ncbi.nlm.nih.gov/pubmed/29333082
http://dx.doi.org/10.7150/ijms.22812
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author Romero-Cara, Patricia
Torres-Moreno, Daniel
Pedregosa, José
Vílchez, Juan Antonio
García-Simón, María Sergia
Ruiz-Merino, Guadalupe
Morán-Sanchez, Senador
Conesa-Zamora, Pablo
author_facet Romero-Cara, Patricia
Torres-Moreno, Daniel
Pedregosa, José
Vílchez, Juan Antonio
García-Simón, María Sergia
Ruiz-Merino, Guadalupe
Morán-Sanchez, Senador
Conesa-Zamora, Pablo
author_sort Romero-Cara, Patricia
collection PubMed
description Background. The production of anti-drug antibodies (ADAs) against IgG monoclonal antibodies (mAbs) targeting tumour necrosis factor (TNF) is an important cause of loss of response to anti-TNF mAbs in patients with inflammatory bowel diseases (IBD) such as Crohn's disease (CD) and ulcerative colitis (UC). Since receptors for the Fc portion of IgG (FCGRs) are involved in the degradation of IgG complexes, we hypothesised that a polymorphism in FCGR3A (V158F; rs396991) gene could be involved in anti-TNF ADA generation and treatment resistance. Material and Methods. A cohort of 103 IBD patients (80 CD, 23 UC) were genotyped and serum level of both anti-TNFs (infliximab or adalimumab) and ADA against them were measured. Results. No significant differences were observed between ADA occurrence or V158F genotype and type of disease or the kind of anti-TNF administrated. Interestingly, VV genotype correlated with patients producing ADA (VV: 37.5% vs. FV: 10.6% or FF: 5%; p=0.004) and was an independent predictor of this event after multivariate analysis. Moreover, VV genotype also correlated with those patients receiving anti-TNF dose intensification (p=0.03). Conclusion. FCGR3A V158F polymorphism seems to be associated with ADA production against mAbs and it could be taken into account when considering the dose and type of anti-TNF in IBD patients.
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spelling pubmed-57657342018-01-14 A FCGR3A Polymorphism Predicts Anti-drug Antibodies in Chronic Inflammatory Bowel Disease Patients Treated With Anti-TNF Romero-Cara, Patricia Torres-Moreno, Daniel Pedregosa, José Vílchez, Juan Antonio García-Simón, María Sergia Ruiz-Merino, Guadalupe Morán-Sanchez, Senador Conesa-Zamora, Pablo Int J Med Sci Research Paper Background. The production of anti-drug antibodies (ADAs) against IgG monoclonal antibodies (mAbs) targeting tumour necrosis factor (TNF) is an important cause of loss of response to anti-TNF mAbs in patients with inflammatory bowel diseases (IBD) such as Crohn's disease (CD) and ulcerative colitis (UC). Since receptors for the Fc portion of IgG (FCGRs) are involved in the degradation of IgG complexes, we hypothesised that a polymorphism in FCGR3A (V158F; rs396991) gene could be involved in anti-TNF ADA generation and treatment resistance. Material and Methods. A cohort of 103 IBD patients (80 CD, 23 UC) were genotyped and serum level of both anti-TNFs (infliximab or adalimumab) and ADA against them were measured. Results. No significant differences were observed between ADA occurrence or V158F genotype and type of disease or the kind of anti-TNF administrated. Interestingly, VV genotype correlated with patients producing ADA (VV: 37.5% vs. FV: 10.6% or FF: 5%; p=0.004) and was an independent predictor of this event after multivariate analysis. Moreover, VV genotype also correlated with those patients receiving anti-TNF dose intensification (p=0.03). Conclusion. FCGR3A V158F polymorphism seems to be associated with ADA production against mAbs and it could be taken into account when considering the dose and type of anti-TNF in IBD patients. Ivyspring International Publisher 2018-01-01 /pmc/articles/PMC5765734/ /pubmed/29333082 http://dx.doi.org/10.7150/ijms.22812 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Romero-Cara, Patricia
Torres-Moreno, Daniel
Pedregosa, José
Vílchez, Juan Antonio
García-Simón, María Sergia
Ruiz-Merino, Guadalupe
Morán-Sanchez, Senador
Conesa-Zamora, Pablo
A FCGR3A Polymorphism Predicts Anti-drug Antibodies in Chronic Inflammatory Bowel Disease Patients Treated With Anti-TNF
title A FCGR3A Polymorphism Predicts Anti-drug Antibodies in Chronic Inflammatory Bowel Disease Patients Treated With Anti-TNF
title_full A FCGR3A Polymorphism Predicts Anti-drug Antibodies in Chronic Inflammatory Bowel Disease Patients Treated With Anti-TNF
title_fullStr A FCGR3A Polymorphism Predicts Anti-drug Antibodies in Chronic Inflammatory Bowel Disease Patients Treated With Anti-TNF
title_full_unstemmed A FCGR3A Polymorphism Predicts Anti-drug Antibodies in Chronic Inflammatory Bowel Disease Patients Treated With Anti-TNF
title_short A FCGR3A Polymorphism Predicts Anti-drug Antibodies in Chronic Inflammatory Bowel Disease Patients Treated With Anti-TNF
title_sort fcgr3a polymorphism predicts anti-drug antibodies in chronic inflammatory bowel disease patients treated with anti-tnf
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765734/
https://www.ncbi.nlm.nih.gov/pubmed/29333082
http://dx.doi.org/10.7150/ijms.22812
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