Radiosensitivity in patients affected by ARPC1B deficiency: a new disease trait?

被引：6

作者：

Chiriaco, Maria ^{[1
]}

Ursu, Giorgiana Madalina ^{[1
,2
]}

Amodio, Donato ^{[3
]}

Cotugno, Nicola ^{[1
,3
]}

Volpi, Stefano ^{[4
]}

Berardinelli, Francesco ^{[5
,6
]}

Pizzi, Simone ^{[7
]}

Cifaldi, Cristina ^{[2
]}

Zoccolillo, Matteo ^{[1
,8
]}

Prigione, Ignazia ^{[4
]}

Di Cesare, Silvia ^{[1
,2
]}

Giancotta, Carmela ^{[3
]}

Anastasio, Elisa ^{[9
]}

Rivalta, Beatrice ^{[1
,2
]}

Pacillo, Lucia ^{[1
,2
]}

Zangari, Paola ^{[3
]}

Fiocchi, Alessandro G. ^{[10
]}

Diociaiuti, Andrea ^{[11
]}

Bruselles, Alessandro ^{[12
]}

Pantaleoni, Francesca ^{[7
]}

Ciolfi, Andrea ^{[7
]}

D'Oria, Valentina ^{[13
]}

Palumbo, Giuseppe ^{[1
,14
]}

Gattorno, Marco ^{[4
]}

El Hachem, Maya ^{[11
]}

de Villartay, Jean-Pierre ^{[15
]}

Finocchi, Andrea ^{[1
,2
]}

Palma, Paolo ^{[1
,3
]}

Rossi, Paolo ^{[1
,2
,3
]}

Tartaglia, Marco ^{[7
]}

Aiuti, Alessandro ^{[8
,16
,17
]}

Antoccia, Antonio ^{[6
]}

Di Matteo, Gigliola ^{[1
,2
]}

Cancrini, Caterina ^{[1
,2
]}

机构：

[1] Univ Roma Tor Vergata, Dept Syst Med, Rome, Italy

[2] Bambino Gesu Pediat Hosp, Sci Inst Res & Healthcare IRCCS, Acad Dept Pediat, Res Unit Primary Immunodeficiencies, Rome, Italy

[3] Bambino Gesu Pediat Hosp, Acad Dept Pediat, Res Unit Clin Immunol & Vaccinol, Rome, Italy

[4] Univ Genoa, Sci Inst Res, Healthcare IRCCS Ist Giannina Gaslini, Ctr Autoinflammatory Dis & Immunodeficiencies, Genoa, Italy

[5] Healthcare IRCCS Santa Lucia Fdn, Sci Inst Res, Lab Neurodev Neurogenet & Mol Neurobiol, Rome, Italy

[6] Roma Tre Univ, Dept Sci, Rome, Italy

[7] Bambino Gesu Pediat Hosp, Sci Inst Res & Healthcare IRCCS, Genet & Rare Dis Res Div, Rome, Italy

[8] San Raffaele Telethon Inst Gene Therapy, Sci Inst Res & Healthcare IRCCS, San Raffaele Sci Inst, Milan, Italy

[9] Magna Graecia Univ Catanzaro, Dept Med & Surg Sci, Pediat Unit, Catanzaro, Italy

[10] Bambino Gesu Pediat Hosp, Sci Inst Res & Healthcare IRCCS, Pediat Allergol Unit, Rome, Italy

[11] Bambino Gesu Pediat Hosp, Sci Inst Res & Healthcare IRCCS, Dermatol Unit, Rome, Italy

[12] Ist Super San, Dept Oncol & Mol Med, Rome, Italy

[13] Bambino Gesu Pediat Hosp, Sci Inst Res & Healthcare IRCCS, Res Labs, Rome, Italy

[14] Bambino Gesu Pediat Hosp, Sci Inst Res & Healthcare IRCCS, Dept Haematol, Rome, Italy

[15] Univ Paris, Imagine Inst, Lab Genome Dynam Immune Syst, INSERM UMR 1163, F-75015 Paris, France

[16] Ist Sci San Raffaele, Pediat Immunohematol, Milan, Italy

[17] Univ Vita Salute San Raffaele, Milan, Italy

来源：

FRONTIERS IN IMMUNOLOGY | 2022年 / 13卷

关键词：

ARPC1B; combined immunodeficiency; immune dysregulation; radiosensitivity; DNA damage response (DDR); PROTEIN; IMMUNODEFICIENCY; LYMPHOCYTES; BIOMARKER; DEFECTS;

D O I：

10.3389/fimmu.2022.919237

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 gamma H2AX 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.

引用

页数：10

共 30 条

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