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Radiosensitivity in patients affected by ARPC1B deficiency: a new disease trait?
Actin-related protein 2/3 complex subunit 1B (ARPC1B) deficiency is a recently described inborn error of immunity (IEI) presenting with combined immunodeficiency and characterized by recurrent infections and thrombocytopenia. Manifestations of immune dysregulation, including colitis, vasculitis, and...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9372879/ https://www.ncbi.nlm.nih.gov/pubmed/35967303 http://dx.doi.org/10.3389/fimmu.2022.919237 |
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author | Chiriaco, Maria Ursu, Giorgiana Madalina Amodio, Donato Cotugno, Nicola Volpi, Stefano Berardinelli, Francesco Pizzi, Simone Cifaldi, Cristina Zoccolillo, Matteo Prigione, Ignazia Di Cesare, Silvia Giancotta, Carmela Anastasio, Elisa Rivalta, Beatrice Pacillo, Lucia Zangari, Paola Fiocchi, Alessandro G. Diociaiuti, Andrea Bruselles, Alessandro Pantaleoni, Francesca Ciolfi, Andrea D’Oria, Valentina Palumbo, Giuseppe Gattorno, Marco El Hachem, Maya de Villartay, Jean-Pierre Finocchi, Andrea Palma, Paolo Rossi, Paolo Tartaglia, Marco Aiuti, Alessandro Antoccia, Antonio Di Matteo, Gigliola Cancrini, Caterina |
author_facet | Chiriaco, Maria Ursu, Giorgiana Madalina Amodio, Donato Cotugno, Nicola Volpi, Stefano Berardinelli, Francesco Pizzi, Simone Cifaldi, Cristina Zoccolillo, Matteo Prigione, Ignazia Di Cesare, Silvia Giancotta, Carmela Anastasio, Elisa Rivalta, Beatrice Pacillo, Lucia Zangari, Paola Fiocchi, Alessandro G. Diociaiuti, Andrea Bruselles, Alessandro Pantaleoni, Francesca Ciolfi, Andrea D’Oria, Valentina Palumbo, Giuseppe Gattorno, Marco El Hachem, Maya de Villartay, Jean-Pierre Finocchi, Andrea Palma, Paolo Rossi, Paolo Tartaglia, Marco Aiuti, Alessandro Antoccia, Antonio Di Matteo, Gigliola Cancrini, Caterina |
author_sort | Chiriaco, Maria |
collection | PubMed |
description | Actin-related protein 2/3 complex subunit 1B (ARPC1B) deficiency is a recently described inborn error of immunity (IEI) presenting with combined immunodeficiency and characterized by recurrent infections and thrombocytopenia. Manifestations of immune dysregulation, including colitis, vasculitis, and severe dermatitis, associated with eosinophilia, hyper-IgA, and hyper-IgE are also described in ARPC1B-deficient patients. To date, hematopoietic stem cell transplantation seems to be the only curative option for patients. ARPC1B is part of the actin-related protein 2/3 complex (Arp2/3) and cooperates with the Wiskott–Aldrich syndrome protein (WASp) in the regulation of the actin cytoskeleton remodeling and in driving double-strand break clustering for homology-directed repair. In this study, we aimed to investigate radiosensitivity (RS) in ARPC1B-deficient patients to assess whether it can be considered an additional disease trait. First, we performed trio-based next-generation-sequencing studies to obtain the ARPC1B molecular diagnosis in our index case characterized by increased RS, and then we confirmed, using three different methods, an increment of radiosensitivity in all enrolled ARPC1B-deficient patients. In particular, higher levels of chromatid-type aberrations and γH2AX foci, with an increased number of cells arrested in the G2/M-phase of the cell cycle, were found in patients’ cells after ionizing radiation exposition and radiomimetic bleomycin treatment. Overall, our data suggest increased radiosensitivity as an additional trait in ARPC1B deficiency and support the necessity to investigate this feature in ARPC1B patients as well as in other IEI with cytoskeleton defects to address specific clinical follow-up and optimize therapeutic interventions. |
format | Online Article Text |
id | pubmed-9372879 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93728792022-08-13 Radiosensitivity in patients affected by ARPC1B deficiency: a new disease trait? Chiriaco, Maria Ursu, Giorgiana Madalina Amodio, Donato Cotugno, Nicola Volpi, Stefano Berardinelli, Francesco Pizzi, Simone Cifaldi, Cristina Zoccolillo, Matteo Prigione, Ignazia Di Cesare, Silvia Giancotta, Carmela Anastasio, Elisa Rivalta, Beatrice Pacillo, Lucia Zangari, Paola Fiocchi, Alessandro G. Diociaiuti, Andrea Bruselles, Alessandro Pantaleoni, Francesca Ciolfi, Andrea D’Oria, Valentina Palumbo, Giuseppe Gattorno, Marco El Hachem, Maya de Villartay, Jean-Pierre Finocchi, Andrea Palma, Paolo Rossi, Paolo Tartaglia, Marco Aiuti, Alessandro Antoccia, Antonio Di Matteo, Gigliola Cancrini, Caterina Front Immunol Immunology Actin-related protein 2/3 complex subunit 1B (ARPC1B) deficiency is a recently described inborn error of immunity (IEI) presenting with combined immunodeficiency and characterized by recurrent infections and thrombocytopenia. Manifestations of immune dysregulation, including colitis, vasculitis, and severe dermatitis, associated with eosinophilia, hyper-IgA, and hyper-IgE are also described in ARPC1B-deficient patients. To date, hematopoietic stem cell transplantation seems to be the only curative option for patients. ARPC1B is part of the actin-related protein 2/3 complex (Arp2/3) and cooperates with the Wiskott–Aldrich syndrome protein (WASp) in the regulation of the actin cytoskeleton remodeling and in driving double-strand break clustering for homology-directed repair. In this study, we aimed to investigate radiosensitivity (RS) in ARPC1B-deficient patients to assess whether it can be considered an additional disease trait. First, we performed trio-based next-generation-sequencing studies to obtain the ARPC1B molecular diagnosis in our index case characterized by increased RS, and then we confirmed, using three different methods, an increment of radiosensitivity in all enrolled ARPC1B-deficient patients. In particular, higher levels of chromatid-type aberrations and γH2AX foci, with an increased number of cells arrested in the G2/M-phase of the cell cycle, were found in patients’ cells after ionizing radiation exposition and radiomimetic bleomycin treatment. Overall, our data suggest increased radiosensitivity as an additional trait in ARPC1B deficiency and support the necessity to investigate this feature in ARPC1B patients as well as in other IEI with cytoskeleton defects to address specific clinical follow-up and optimize therapeutic interventions. Frontiers Media S.A. 2022-07-29 /pmc/articles/PMC9372879/ /pubmed/35967303 http://dx.doi.org/10.3389/fimmu.2022.919237 Text en Copyright © 2022 Chiriaco, Ursu, Amodio, Cotugno, Volpi, Berardinelli, Pizzi, Cifaldi, Zoccolillo, Prigione, Di Cesare, Giancotta, Anastasio, Rivalta, Pacillo, Zangari, Fiocchi, Diociaiuti, Bruselles, Pantaleoni, Ciolfi, D’Oria, Palumbo, Gattorno, El Hachem, de Villartay, Finocchi, Palma, Rossi, Tartaglia, Aiuti, Antoccia, Di Matteo and Cancrini 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 | Immunology Chiriaco, Maria Ursu, Giorgiana Madalina Amodio, Donato Cotugno, Nicola Volpi, Stefano Berardinelli, Francesco Pizzi, Simone Cifaldi, Cristina Zoccolillo, Matteo Prigione, Ignazia Di Cesare, Silvia Giancotta, Carmela Anastasio, Elisa Rivalta, Beatrice Pacillo, Lucia Zangari, Paola Fiocchi, Alessandro G. Diociaiuti, Andrea Bruselles, Alessandro Pantaleoni, Francesca Ciolfi, Andrea D’Oria, Valentina Palumbo, Giuseppe Gattorno, Marco El Hachem, Maya de Villartay, Jean-Pierre Finocchi, Andrea Palma, Paolo Rossi, Paolo Tartaglia, Marco Aiuti, Alessandro Antoccia, Antonio Di Matteo, Gigliola Cancrini, Caterina Radiosensitivity in patients affected by ARPC1B deficiency: a new disease trait? |
title | Radiosensitivity in patients affected by ARPC1B deficiency: a new disease trait? |
title_full | Radiosensitivity in patients affected by ARPC1B deficiency: a new disease trait? |
title_fullStr | Radiosensitivity in patients affected by ARPC1B deficiency: a new disease trait? |
title_full_unstemmed | Radiosensitivity in patients affected by ARPC1B deficiency: a new disease trait? |
title_short | Radiosensitivity in patients affected by ARPC1B deficiency: a new disease trait? |
title_sort | radiosensitivity in patients affected by arpc1b deficiency: a new disease trait? |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9372879/ https://www.ncbi.nlm.nih.gov/pubmed/35967303 http://dx.doi.org/10.3389/fimmu.2022.919237 |
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