Frontiers in Immunology (Jul 2022)
Radiosensitivity in patients affected by ARPC1B deficiency: a new disease trait?
- Maria Chiriaco,
- Giorgiana Madalina Ursu,
- Giorgiana Madalina Ursu,
- Donato Amodio,
- Nicola Cotugno,
- Nicola Cotugno,
- Stefano Volpi,
- Francesco Berardinelli,
- Francesco Berardinelli,
- Simone Pizzi,
- Cristina Cifaldi,
- Matteo Zoccolillo,
- Matteo Zoccolillo,
- Ignazia Prigione,
- Silvia Di Cesare,
- Silvia Di Cesare,
- Carmela Giancotta,
- Elisa Anastasio,
- Beatrice Rivalta,
- Beatrice Rivalta,
- Lucia Pacillo,
- Lucia Pacillo,
- Paola Zangari,
- Alessandro G. Fiocchi,
- Andrea Diociaiuti,
- Alessandro Bruselles,
- Francesca Pantaleoni,
- Andrea Ciolfi,
- Valentina D’Oria,
- Giuseppe Palumbo,
- Giuseppe Palumbo,
- Marco Gattorno,
- Maya El Hachem,
- Jean-Pierre de Villartay,
- Andrea Finocchi,
- Andrea Finocchi,
- Paolo Palma,
- Paolo Palma,
- Paolo Rossi,
- Paolo Rossi,
- Paolo Rossi,
- Marco Tartaglia,
- Alessandro Aiuti,
- Alessandro Aiuti,
- Alessandro Aiuti,
- Antonio Antoccia,
- Gigliola Di Matteo,
- Gigliola Di Matteo,
- Caterina Cancrini,
- Caterina Cancrini
Affiliations
- Maria Chiriaco
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- Giorgiana Madalina Ursu
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- Giorgiana Madalina Ursu
- Academic department of Pediatrics, Research Unit of Primary Immunodeficiencies, Bambino Gesù Children’s Hospital, Scientific Institute for Research and Healthcare (IRCCS), Rome, Italy
- Donato Amodio
- Academic Department of Pediatrics, Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children’s Hospital, Rome, Italy
- Nicola Cotugno
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- Nicola Cotugno
- Academic Department of Pediatrics, Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children’s Hospital, Rome, Italy
- Stefano Volpi
- Center for Autoinflammatory Diseases and Immunodeficiencies, Scientific Institute for Research and Healthcare (IRCCS) Istituto Giannina Gaslini and University of Genoa, Genoa, Italy
- Francesco Berardinelli
- Laboratory of Neurodevelopment, Neurogenetics and Molecular Neurobiology, Scientific Institute for Research and Healthcare (IRCCS) Santa Lucia Foundation, Rome, Italy
- Francesco Berardinelli
- Department of Science, Roma Tre University, Rome, Italy
- Simone Pizzi
- Genetics and Rare Diseases Research Division, Bambino Gesù Children’s Hospital, Scientific Institute for Research and Healthcare (IRCCS), Rome, Italy
- Cristina Cifaldi
- Academic department of Pediatrics, Research Unit of Primary Immunodeficiencies, Bambino Gesù Children’s Hospital, Scientific Institute for Research and Healthcare (IRCCS), Rome, Italy
- Matteo Zoccolillo
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- Matteo Zoccolillo
- San Raffaele Telethon Institute for Gene Therapy, Scientific Institute for Research and Healthcare (IRCCS), San Raffaele Scientific Institute, Milan, Italy
- Ignazia Prigione
- Center for Autoinflammatory Diseases and Immunodeficiencies, Scientific Institute for Research and Healthcare (IRCCS) Istituto Giannina Gaslini and University of Genoa, Genoa, Italy
- Silvia Di Cesare
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- Silvia Di Cesare
- Academic department of Pediatrics, Research Unit of Primary Immunodeficiencies, Bambino Gesù Children’s Hospital, Scientific Institute for Research and Healthcare (IRCCS), Rome, Italy
- Carmela Giancotta
- Academic Department of Pediatrics, Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children’s Hospital, Rome, Italy
- Elisa Anastasio
- Department of Medical and Surgical Sciences, Pediatrics Unit, University “Magna Graecia”, Catanzaro, Italy
- Beatrice Rivalta
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- Beatrice Rivalta
- Academic department of Pediatrics, Research Unit of Primary Immunodeficiencies, Bambino Gesù Children’s Hospital, Scientific Institute for Research and Healthcare (IRCCS), Rome, Italy
- Lucia Pacillo
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- Lucia Pacillo
- Academic department of Pediatrics, Research Unit of Primary Immunodeficiencies, Bambino Gesù Children’s Hospital, Scientific Institute for Research and Healthcare (IRCCS), Rome, Italy
- Paola Zangari
- Academic Department of Pediatrics, Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children’s Hospital, Rome, Italy
- Alessandro G. Fiocchi
- 0Pediatric Allergology Unit, Bambino Gesù Children’s Hospital, Scientific Institute for Research and Healthcare (IRCCS), Rome, Italy
- Andrea Diociaiuti
- 1Dermatology Unit, Bambino Gesù Children’s Hospital, Scientific Institute for Research and Healthcare (IRCCS), Rome, Italy
- Alessandro Bruselles
- 2Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy
- Francesca Pantaleoni
- Genetics and Rare Diseases Research Division, Bambino Gesù Children’s Hospital, Scientific Institute for Research and Healthcare (IRCCS), Rome, Italy
- Andrea Ciolfi
- Genetics and Rare Diseases Research Division, Bambino Gesù Children’s Hospital, Scientific Institute for Research and Healthcare (IRCCS), Rome, Italy
- Valentina D’Oria
- 3Research Laboratories, Bambino Gesù Children’s Hospital, Scientific Institute for Research and Healthcare (IRCCS), Rome, Italy
- Giuseppe Palumbo
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- Giuseppe Palumbo
- 4Department of Haematology, Bambino Gesù Children’s Hospital, Scientific Institute for Research and Healthcare (IRCCS), Rome, Italy
- Marco Gattorno
- Center for Autoinflammatory Diseases and Immunodeficiencies, Scientific Institute for Research and Healthcare (IRCCS) Istituto Giannina Gaslini and University of Genoa, Genoa, Italy
- Maya El Hachem
- 1Dermatology Unit, Bambino Gesù Children’s Hospital, Scientific Institute for Research and Healthcare (IRCCS), Rome, Italy
- Jean-Pierre de Villartay
- 5Université de Paris, Imagine Institute, Laboratory “Genome Dynamics in the Immune System”, INSERM UMR 1163, F-75015, Paris, France
- Andrea Finocchi
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- Andrea Finocchi
- Academic department of Pediatrics, Research Unit of Primary Immunodeficiencies, Bambino Gesù Children’s Hospital, Scientific Institute for Research and Healthcare (IRCCS), Rome, Italy
- Paolo Palma
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- Paolo Palma
- Academic Department of Pediatrics, Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children’s Hospital, Rome, Italy
- Paolo Rossi
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- Paolo Rossi
- Academic department of Pediatrics, Research Unit of Primary Immunodeficiencies, Bambino Gesù Children’s Hospital, Scientific Institute for Research and Healthcare (IRCCS), Rome, Italy
- Paolo Rossi
- Academic Department of Pediatrics, Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children’s Hospital, Rome, Italy
- Marco Tartaglia
- Genetics and Rare Diseases Research Division, Bambino Gesù Children’s Hospital, Scientific Institute for Research and Healthcare (IRCCS), Rome, Italy
- Alessandro Aiuti
- San Raffaele Telethon Institute for Gene Therapy, Scientific Institute for Research and Healthcare (IRCCS), San Raffaele Scientific Institute, Milan, Italy
- Alessandro Aiuti
- 6Pediatric Immunohematology, San Raffaele Scientific Institute, Milan, Italy
- Alessandro Aiuti
- 7Vita Salute San Raffaele University, Milan, Italy
- Antonio Antoccia
- Department of Science, Roma Tre University, Rome, Italy
- Gigliola Di Matteo
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- Gigliola Di Matteo
- Academic department of Pediatrics, Research Unit of Primary Immunodeficiencies, Bambino Gesù Children’s Hospital, Scientific Institute for Research and Healthcare (IRCCS), Rome, Italy
- Caterina Cancrini
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- Caterina Cancrini
- Academic department of Pediatrics, Research Unit of Primary Immunodeficiencies, Bambino Gesù Children’s Hospital, Scientific Institute for Research and Healthcare (IRCCS), Rome, Italy
- DOI
- https://doi.org/10.3389/fimmu.2022.919237
- Journal volume & issue
-
Vol. 13
Abstract
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.
Keywords
