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Ig Glycosylation in Ulcerative Colitis: It’s Time for New Biomarkers

Background: Ulcerative colitis (UC) is a chronic relapsing disease, which needs a continue monitoring, especially during biological therapies. An increasing number of patients is treated with anti-Tumor Necrosis factor (TNF) drugs, and current research is focalized to identify biomarkers able to mon...

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Autores principales: Capecchi, Riccardo, Migliorini, Paola, Zanzi, Federico, Maltinti, Simona, Puxeddu, Ilaria, de Bortoli, Nicola, Bellini, Massimo, Costa, Francesco, Marchi, Santino, Bertani, Lorenzo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062917/
https://www.ncbi.nlm.nih.gov/pubmed/33897440
http://dx.doi.org/10.3389/fphar.2021.654319
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author Capecchi, Riccardo
Migliorini, Paola
Zanzi, Federico
Maltinti, Simona
Puxeddu, Ilaria
de Bortoli, Nicola
Bellini, Massimo
Costa, Francesco
Marchi, Santino
Bertani, Lorenzo
author_facet Capecchi, Riccardo
Migliorini, Paola
Zanzi, Federico
Maltinti, Simona
Puxeddu, Ilaria
de Bortoli, Nicola
Bellini, Massimo
Costa, Francesco
Marchi, Santino
Bertani, Lorenzo
author_sort Capecchi, Riccardo
collection PubMed
description Background: Ulcerative colitis (UC) is a chronic relapsing disease, which needs a continue monitoring, especially during biological therapies. An increasing number of patients is treated with anti-Tumor Necrosis factor (TNF) drugs, and current research is focalized to identify biomarkers able to monitor the disease and to predict therapeutic outcome. Methods: We enrolled consecutive UC patients treated with anti-TNF, naïve to biologic drugs. Therapeutic outcome was evaluated after 54 weeks of treatment in terms of clinical remission (Partial Mayo Score -PMS- <2) and mucosal healing (Mayo Endoscopic Score <2). On serum samples collected at baseline and after 54 weeks of treatment, a Lectin-based ELISA assay was performed, and specific glycosylation patterns were evaluated by biotin-labelled lectins. We have also collected 21 healthy controls (NHS) samples, age and sex-matched. Results: Out of 44 UC patients enrolled, 22 achieved clinical remission and mucosal healing after 54 weeks. At baseline, when Protein A was used as coating, UC patients non-responders showed a reduced reactivity to Jacalin (JAC) in comparison with NHS (p = 0.04). After one year of treatment, a decrease in JAC binding was seen only in responders, in comparison with baseline (p = 0.04). When JAC binding was tested selecting IgG by means of Fab anti-IgG Fab, UC patients displayed an increased reactivity after anti-TNF therapy (p < 0,0001 vs controls). At baseline, PMS inversely correlates with JAC binding when Fab anti-IgG Fab was used in solid phase (r (2) = 0,2211; p = 0,0033). Patients with higher PMS at baseline (PMS ≥5) presented lower binding capacity for JAC in comparison with NHS and with lower PMS patients (p = 0,0135 and p = 0,0089, respectively). Conclusion: Ig glycosylation was correlated with clinical and endoscopic activity in patients with UC. JAC protein A-selected Ig showed a possible role in predicting therapeutic effectiveness. If these data would be confirmed, Ig glycosylation could be used as biomarker in UC.
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spelling pubmed-80629172021-04-24 Ig Glycosylation in Ulcerative Colitis: It’s Time for New Biomarkers Capecchi, Riccardo Migliorini, Paola Zanzi, Federico Maltinti, Simona Puxeddu, Ilaria de Bortoli, Nicola Bellini, Massimo Costa, Francesco Marchi, Santino Bertani, Lorenzo Front Pharmacol Pharmacology Background: Ulcerative colitis (UC) is a chronic relapsing disease, which needs a continue monitoring, especially during biological therapies. An increasing number of patients is treated with anti-Tumor Necrosis factor (TNF) drugs, and current research is focalized to identify biomarkers able to monitor the disease and to predict therapeutic outcome. Methods: We enrolled consecutive UC patients treated with anti-TNF, naïve to biologic drugs. Therapeutic outcome was evaluated after 54 weeks of treatment in terms of clinical remission (Partial Mayo Score -PMS- <2) and mucosal healing (Mayo Endoscopic Score <2). On serum samples collected at baseline and after 54 weeks of treatment, a Lectin-based ELISA assay was performed, and specific glycosylation patterns were evaluated by biotin-labelled lectins. We have also collected 21 healthy controls (NHS) samples, age and sex-matched. Results: Out of 44 UC patients enrolled, 22 achieved clinical remission and mucosal healing after 54 weeks. At baseline, when Protein A was used as coating, UC patients non-responders showed a reduced reactivity to Jacalin (JAC) in comparison with NHS (p = 0.04). After one year of treatment, a decrease in JAC binding was seen only in responders, in comparison with baseline (p = 0.04). When JAC binding was tested selecting IgG by means of Fab anti-IgG Fab, UC patients displayed an increased reactivity after anti-TNF therapy (p < 0,0001 vs controls). At baseline, PMS inversely correlates with JAC binding when Fab anti-IgG Fab was used in solid phase (r (2) = 0,2211; p = 0,0033). Patients with higher PMS at baseline (PMS ≥5) presented lower binding capacity for JAC in comparison with NHS and with lower PMS patients (p = 0,0135 and p = 0,0089, respectively). Conclusion: Ig glycosylation was correlated with clinical and endoscopic activity in patients with UC. JAC protein A-selected Ig showed a possible role in predicting therapeutic effectiveness. If these data would be confirmed, Ig glycosylation could be used as biomarker in UC. Frontiers Media S.A. 2021-04-09 /pmc/articles/PMC8062917/ /pubmed/33897440 http://dx.doi.org/10.3389/fphar.2021.654319 Text en Copyright © 2021 Capecchi, Migliorini, Zanzi, Maltinti, Puxeddu, de Bortoli, Bellini, Costa, Marchi and Bertani. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Capecchi, Riccardo
Migliorini, Paola
Zanzi, Federico
Maltinti, Simona
Puxeddu, Ilaria
de Bortoli, Nicola
Bellini, Massimo
Costa, Francesco
Marchi, Santino
Bertani, Lorenzo
Ig Glycosylation in Ulcerative Colitis: It’s Time for New Biomarkers
title Ig Glycosylation in Ulcerative Colitis: It’s Time for New Biomarkers
title_full Ig Glycosylation in Ulcerative Colitis: It’s Time for New Biomarkers
title_fullStr Ig Glycosylation in Ulcerative Colitis: It’s Time for New Biomarkers
title_full_unstemmed Ig Glycosylation in Ulcerative Colitis: It’s Time for New Biomarkers
title_short Ig Glycosylation in Ulcerative Colitis: It’s Time for New Biomarkers
title_sort ig glycosylation in ulcerative colitis: it’s time for new biomarkers
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062917/
https://www.ncbi.nlm.nih.gov/pubmed/33897440
http://dx.doi.org/10.3389/fphar.2021.654319
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