{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T01:26:42Z","timestamp":1787794002455,"version":"build-2784847793"},"reference-count":71,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T00:00:00Z","timestamp":1737936000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T00:00:00Z","timestamp":1737936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Rheumatol"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Type I interferonopathies including Aicardi-Gouti\u00e9res Syndrome (AGS) represent a heterogeneous group of clinical phenotypes. Herein, we present a Case with combined AGS and Cornelia de Lange Syndrome (CdLS)\u2014a cohesinopathy\u2014with comprehensive analysis of the immune and genomic abnormalities.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Case and methods<\/jats:title>\n            <jats:p>A 20-year old man presented with chilblain lesions and resorption of distal phalanges of fingers and toes, somatic and psychomotor retardation, microcephaly, synophrys, hearing losing and other aberrancies consistent with the phenotype of CdLS. We used whole exome sequencing to genetically map the associated mutations and performed transcriptome profiling and enrichment analysis in CD14<jats:sup>+<\/jats:sup> monocytes of the patient and immune phenotyping by mass cytometry (CyToF), comparing to healthy individuals and lupus patients as disease controls. DNA damage response was assayed by confocal microscopy in the peripheral blood of this patient.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Next generation exome sequencing confirmed a homozygous SAMHD1 gene mutation and a hemizygous non-synonymous mutation on SMC1A gene, responsible for the AGS and CdLS, respectively. Transcriptome profiling of CD14<jats:sup>+<\/jats:sup> monocytes of the patient showed enrichment of type I IFN signaling and enhanced DNA damage response pathway. Broad immune phenotype of the peripheral blood of the patient revealed absence of activated T cell populations, increased frequency of NK cells and plasmablasts and enhanced granulocytic lineage. Further analysis suggested activation of the ATM branch of DNA damage response and increased apoptosis in the periphery of the patient.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>A rare case of a patient bearing two genetic lesions (responsible for AGS\/CdLS syndromes) exhibits distinctive features of genomic damage and interferon responses. Immune phenotype revealed granulocytic skewing and absence of activated T cells compatible with chronic antigenic stimulation and\/or homing of these cells at sites of inflammation.\n<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12969-024-01050-7","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T07:39:50Z","timestamp":1737963590000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Increased interferon I signaling, DNA damage response and evidence of T-cell exhaustion in a patient with combined interferonopathy (Aicardi-Gouti\u00e8res Syndrome, AGS) and cohesinopathy (Cornelia de Lange Syndrome, CdLS)"],"prefix":"10.1186","volume":"23","author":[{"given":"Sorina","family":"Boiu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Paschalidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Sentis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodora","family":"Manolakou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrianos","family":"Nezos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manolis","family":"Gialitakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Grigoriou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erato","family":"Atsali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melpomeni","family":"Giorgi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Argirios","family":"Ntinopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clio","family":"Mavragani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Periklis","family":"Makrythanasis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios T.","family":"Boumpas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5647-6505","authenticated-orcid":false,"given":"Aggelos","family":"Banos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,27]]},"reference":[{"issue":"2","key":"1050_CR1","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1002\/ajmg.a.36887","volume":"167A","author":"YJ Crow","year":"2015","unstructured":"Crow YJ, Chase DS, Lowenstein Schmidt J, Szynkiewicz M, Forte GM, Gornall HL, Oojageer A, Anderson B, Pizzino A, Helman G, et al. Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1. Am J Med Genet A. 2015;167A(2):296\u2013312.","journal-title":"Am J Med Genet A"},{"issue":"12","key":"1050_CR2","doi-asserted-by":"publisher","first-page":"1364","DOI":"10.1038\/s41588-020-00737-3","volume":"52","author":"C Uggenti","year":"2020","unstructured":"Uggenti C, Lepelley A, Depp M, Badrock AP, Rodero MP, El-Daher MT, Rice GI, Dhir S, Wheeler AP, Dhir A, et al. cGAS-mediated induction of type I interferon due to inborn errors of histone pre-mRNA processing. Nat Genet. 2020;52(12):1364\u201372.","journal-title":"Nat Genet"},{"issue":"7","key":"1050_CR3","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1007\/s12519-022-00679-2","volume":"19","author":"GB Dell\u2019Isola","year":"2023","unstructured":"Dell\u2019Isola GB, Dini G, Culpepper KL, Portwood KE, Ferrara P, Di Cara G, Verrotti A, Lodolo M. Clinical spectrum and currently available treatment of type I interferonopathy Aicardi-Goutieres Syndrome. World J Pediatr. 2023;19(7):635\u201343.","journal-title":"World J Pediatr"},{"issue":"10","key":"1050_CR4","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1038\/s41576-018-0031-0","volume":"19","author":"AD Kline","year":"2018","unstructured":"Kline AD, Moss JF, Selicorni A, Bisgaard AM, Deardorff MA, Gillett PM, Ishman SL, Kerr LM, Levin AV, Mulder PA, et al. Diagnosis and management of Cornelia de Lange Syndrome: first international consensus statement. Nat Rev Genet. 2018;19(10):649\u201366.","journal-title":"Nat Rev Genet"},{"key":"1050_CR5","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.semcdb.2018.08.004","volume":"90","author":"Z Zhu","year":"2019","unstructured":"Zhu Z, Wang X. Roles of cohesin in chromosome architecture and gene expression. Semin Cell Dev Biol. 2019;90:187\u201393.","journal-title":"Semin Cell Dev Biol"},{"issue":"22","key":"1050_CR6","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.1056\/NEJMc2031081","volume":"383","author":"B Neven","year":"2020","unstructured":"Neven B, Al Adba B, Hully M, Desguerre I, Pressiat C, Boddaert N, Duffy D, Rice GI, Seabra L, Fremond ML, et al. JAK inhibition in the Aicardi-Goutieres Syndrome. N Engl J Med. 2020;383(22):2190\u20131.","journal-title":"N Engl J Med"},{"issue":"10","key":"1050_CR7","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1056\/NEJMc2001362","volume":"383","author":"A Vanderver","year":"2020","unstructured":"Vanderver A, Adang L, Gavazzi F, McDonald K, Helman G, Frank DB, Jaffe N, Yum SW, Collins A, Keller SR, et al. Janus kinase inhibition in the Aicardi-Goutieres Syndrome. N Engl J Med. 2020;383(10):986\u20139.","journal-title":"N Engl J Med"},{"key":"1050_CR8","doi-asserted-by":"publisher","first-page":"725868","DOI":"10.3389\/fped.2021.725868","volume":"9","author":"M Cattalini","year":"2021","unstructured":"Cattalini M, Galli J, Zunica F, Ferraro RM, Carpanelli M, Orcesi S, Palumbo G, Pinelli L, Giliani S, Fazzi E, Badolato R. Case report: the JAK-Inhibitor Ruxolitinib use in Aicardi-Goutieres Syndrome due to ADAR1 mutation. Front Pediatr. 2021;9:725868.","journal-title":"Front Pediatr"},{"issue":"23","key":"1050_CR9","doi-asserted-by":"publisher","first-page":"2275","DOI":"10.1056\/NEJMc1810983","volume":"379","author":"GI Rice","year":"2018","unstructured":"Rice GI, Meyzer C, Bouazza N, Hully M, Boddaert N, Semeraro M, Zeef LAH, Rozenberg F, Bondet V, Duffy D, et al. Reverse-transcriptase inhibitors in the Aicardi-Goutieres Syndrome. N Engl J Med. 2018;379(23):2275\u20137.","journal-title":"N Engl J Med"},{"issue":"6","key":"1050_CR10","doi-asserted-by":"publisher","first-page":"1540","DOI":"10.1093\/hmg\/ddu565","volume":"24","author":"B Xu","year":"2015","unstructured":"Xu B, Sowa N, Cardenas ME, Gerton JL. L-leucine partially rescues translational and developmental defects associated with zebrafish models of Cornelia de Lange Syndrome. Hum Mol Genet. 2015;24(6):1540\u201355.","journal-title":"Hum Mol Genet"},{"issue":"14","key":"1050_CR11","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","volume":"25","author":"H Li","year":"2009","unstructured":"Li H, Durbin R. Fast and accurate short read alignment with burrows-wheeler transform. Bioinformatics. 2009;25(14):1754\u201360.","journal-title":"Bioinformatics"},{"issue":"16","key":"1050_CR12","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","volume":"25","author":"H Li","year":"2009","unstructured":"Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R. Genome Project Data Processing S: The sequence alignment\/map format and SAMtools. Bioinformatics. 2009;25(16):2078\u20139.","journal-title":"Bioinformatics"},{"issue":"9","key":"1050_CR13","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1101\/gr.107524.110","volume":"20","author":"A McKenna","year":"2010","unstructured":"McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, Garimella K, Altshuler D, Gabriel S, Daly M, DePristo MA. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010;20(9):1297\u2013303.","journal-title":"Genome Res"},{"issue":"16","key":"1050_CR14","doi-asserted-by":"publisher","first-page":"e164","DOI":"10.1093\/nar\/gkq603","volume":"38","author":"K Wang","year":"2010","unstructured":"Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010;38(16):e164.","journal-title":"Nucleic Acids Res"},{"key":"1050_CR15","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.jaut.2015.07.002","volume":"63","author":"A Nezos","year":"2015","unstructured":"Nezos A, Gravani F, Tassidou A, Kapsogeorgou EK, Voulgarelis M, Koutsilieris M, Crow MK, Mavragani CP. Type I and II interferon signatures in Sjogren\u2019s Syndrome pathogenesis: contributions in distinct clinical phenotypes and Sjogren\u2019s related lymphomagenesis. J Autoimmun. 2015;63:47\u201358.","journal-title":"J Autoimmun"},{"key":"1050_CR16","unstructured":"Andrews S: FastQC: a quality control tool for high throughput sequence data. In.: Cambridge, United Kingdom; 2010."},{"issue":"1","key":"1050_CR17","doi-asserted-by":"publisher","first-page":"10","DOI":"10.14806\/ej.17.1.200","volume":"17","author":"M Martin","year":"2011","unstructured":"Martin M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet journal. 2011;17(1):10\u20132.","journal-title":"EMBnet journal"},{"issue":"1","key":"1050_CR18","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M, Gingeras TR. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29(1):15\u201321.","journal-title":"Bioinformatics"},{"issue":"D1","key":"1050_CR19","doi-asserted-by":"publisher","first-page":"D916","DOI":"10.1093\/nar\/gkaa1087","volume":"49","author":"A Frankish","year":"2021","unstructured":"Frankish A, Diekhans M, Jungreis I, Lagarde J, Loveland JE, Mudge JM, Sisu C, Wright JC, Armstrong J, Barnes I. GENCODE 2021. Nucleic Acids Res. 2021;49(D1):D916\u201323.","journal-title":"Nucleic Acids Res"},{"issue":"2","key":"1050_CR20","doi-asserted-by":"publisher","first-page":"giab008","DOI":"10.1093\/gigascience\/giab008","volume":"10","author":"P Danecek","year":"2021","unstructured":"Danecek P, Bonfield JK, Liddle J, Marshall J, Ohan V, Pollard MO, Whitwham A, Keane T, McCarthy SA, Davies RM, Li H. Twelve years of SAMtools and BCFtools. Gigascience. 2021;10(2):giab008.","journal-title":"Gigascience"},{"issue":"2","key":"1050_CR21","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","volume":"31","author":"S Anders","year":"2015","unstructured":"Anders S, Pyl PT, Huber W. HTSeq\u2014a Python framework to work with high-throughput sequencing data. Bioinformatics. 2015;31(2):166\u20139.","journal-title":"Bioinformatics."},{"key":"1050_CR22","doi-asserted-by":"publisher","first-page":"1203848","DOI":"10.3389\/fimmu.2023.1203848","volume":"14","author":"G Sentis","year":"2023","unstructured":"Sentis G, Loukogiannaki C, Malissovas N, Nikolopoulos D, Manolakou T, Flouda S, Grigoriou M, Banos A, Boumpas DT, Filia A. A network-based approach reveals long non-coding RNAs associated with disease activity in lupus nephritis: key pathways for flare and potential biomarkers to be used as liquid biopsies. Front Immunol. 2023;14:1203848.","journal-title":"Front Immunol"},{"issue":"1","key":"1050_CR23","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","volume":"26","author":"MD Robinson","year":"2010","unstructured":"Robinson MD, McCarthy DJ, Smyth GK. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2010;26(1):139\u201340.","journal-title":"Bioinformatics"},{"key":"1050_CR24","unstructured":"Team RC: R: A language and environment for statistical computing. URL. R Foundation for Statistical Computing: Vienna, Austria 2021."},{"key":"1050_CR25","doi-asserted-by":"crossref","unstructured":"Wickham H. Mastering the grammar. ggplot2: elegant graphics for data analysis 2009:27\u201340.\u00a0https:\/\/link.springer.com\/book\/10.1007\/978-0-387-98141-3.","DOI":"10.1007\/978-0-387-98141-3_3"},{"issue":"18","key":"1050_CR26","doi-asserted-by":"publisher","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","volume":"32","author":"Z Gu","year":"2016","unstructured":"Gu Z, Eils R, Schlesner M. Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics. 2016;32(18):2847\u20139.","journal-title":"Bioinformatics"},{"issue":"6","key":"1050_CR27","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","volume":"1","author":"A Liberzon","year":"2015","unstructured":"Liberzon A, Birger C, Thorvaldsd\u00f3ttir H, Ghandi M, Mesirov JP, Tamayo P. The molecular signatures database hallmark gene set collection. Cell Syst. 2015;1(6):417\u201325.","journal-title":"Cell Syst"},{"issue":"43","key":"1050_CR28","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","volume":"102","author":"A Subramanian","year":"2005","unstructured":"Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci. 2005;102(43):15545\u201350.","journal-title":"Proc Natl Acad Sci"},{"key":"1050_CR29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2105-14-7","volume":"14","author":"S H\u00e4nzelmann","year":"2013","unstructured":"H\u00e4nzelmann S, Castelo R, Guinney J. GSVA: gene set variation analysis for microarray and RNA-seq data. BMC Bioinformatics. 2013;14:1\u201315.","journal-title":"BMC Bioinformatics"},{"issue":"6","key":"1050_CR30","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.1002\/art.38628","volume":"66","author":"L Chiche","year":"2014","unstructured":"Chiche L, Jourde-Chiche N, Whalen E, Presnell S, Gersuk V, Dang K, Anguiano E, Quinn C, Burtey S, Berland Y. Modular transcriptional repertoire analyses of adults with systemic lupus erythematosus reveal distinct type I and type II interferon signatures. Arthritis Rheumatol. 2014;66(6):1583\u201395.","journal-title":"Arthritis Rheumatol"},{"key":"1050_CR31","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1071623","volume":"14","author":"AG Vakrakou","year":"2023","unstructured":"Vakrakou AG, Paschalidis N, Pavlos E, Giannouli C, Karathanasis D, Tsipota X, Velonakis G, Stadelmann-Nessler C, Evangelopoulos M-E, Stefanis L. Specific myeloid signatures in peripheral blood differentiate active and rare clinical phenotypes of multiple sclerosis. Front Immunol. 2023;14: 1071623.","journal-title":"Front Immunol"},{"key":"1050_CR32","doi-asserted-by":"crossref","unstructured":"Nowicka M, Krieg C, Crowell HL, Weber LM, Hartmann FJ, Guglietta S, Becher B, Levesque MP, Robinson MD: CyTOF workflow: differential discovery in high-throughput high-dimensional cytometry datasets. F1000Res 2017, 6:748.","DOI":"10.12688\/f1000research.11622.2"},{"issue":"2","key":"1050_CR33","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1002\/cyto.b.21858","volume":"98","author":"CB Bagwell","year":"2020","unstructured":"Bagwell CB, Hunsberger B, Hill B, Herbert D, Bray C, Selvanantham T, Li S, Villasboas JC, Pavelko K, Strausbauch M, et al. Multi-site reproducibility of a human immunophenotyping assay in whole blood and peripheral blood mononuclear cells preparations using CyTOF technology coupled with Maxpar Pathsetter, an automated data analysis system. Cytometry B Clin Cytom. 2020;98(2):146\u201360.","journal-title":"Cytometry B Clin Cytom"},{"issue":"5","key":"1050_CR34","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1002\/cyto.a.24317","volume":"99","author":"D Geanon","year":"2021","unstructured":"Geanon D, Lee B, Gonzalez-Kozlova E, Kelly G, Handler D, Upadhyaya B, Leech J, De Real RM, Herbinet M, Magen A, et al. A streamlined whole blood CyTOF workflow defines a circulating immune cell signature of COVID-19. Cytometry A. 2021;99(5):446\u201361.","journal-title":"Cytometry A"},{"issue":"7","key":"1050_CR35","doi-asserted-by":"publisher","first-page":"2789","DOI":"10.1172\/JCI92079","volume":"127","author":"T Alissafi","year":"2017","unstructured":"Alissafi T, Banos A, Boon L, Sparwasser T, Ghigo A, Wing K, Vassilopoulos D, Boumpas D, Chavakis T, Cadwell K, Verginis P. Tregs restrain dendritic cell autophagy to ameliorate autoimmunity. J Clin Invest. 2017;127(7):2789\u2013804.","journal-title":"J Clin Invest"},{"key":"1050_CR36","doi-asserted-by":"publisher","first-page":"109765","DOI":"10.1016\/j.clim.2023.109765","volume":"255","author":"EM Stergioti","year":"2023","unstructured":"Stergioti EM, Manolakou T, Sentis G, Samiotaki M, Kapsala N, Fanouriakis A, Boumpas DT, Banos A. Transcriptomic and proteomic profiling reveals distinct pathogenic features of peripheral non-classical monocytes in systemic lupus erythematosus. Clin Immunol. 2023;255:109765.","journal-title":"Clin Immunol"},{"issue":"11","key":"1050_CR37","doi-asserted-by":"publisher","first-page":"2820","DOI":"10.3390\/biomedicines10112820","volume":"10","author":"EM Stergioti","year":"2022","unstructured":"Stergioti EM, Manolakou T, Boumpas DT, Banos A. Antiviral innate immune responses in autoimmunity: receptors, pathways, and therapeutic targeting. Biomedicines. 2022;10(11):2820.","journal-title":"Biomedicines"},{"issue":"43","key":"1050_CR38","doi-asserted-by":"publisher","first-page":"eabo5840","DOI":"10.1126\/sciadv.abo5840","volume":"8","author":"T Manolakou","year":"2022","unstructured":"Manolakou T, Nikolopoulos D, Gkikas D, Filia A, Samiotaki M, Stamatakis G, Fanouriakis A, Politis P, Banos A, Alissafi T, et al. ATR-mediated DNA damage responses underlie aberrant B cell activity in systemic lupus erythematosus. Sci Adv. 2022;8(43):eabo5840.","journal-title":"Sci Adv"},{"key":"1050_CR39","doi-asserted-by":"crossref","unstructured":"Galita G, Brzezinska O, Gulbas I, Sarnik J, Poplawska M, Makowska J, Poplawski T: Increased sensitivity of PBMCs isolated from patients with rheumatoid arthritis to DNA damaging agents is connected with inefficient DNA repair. J Clin Med. 2020;9(4).","DOI":"10.3390\/jcm9040988"},{"key":"1050_CR40","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.clim.2019.03.009","volume":"203","author":"VL Souliotis","year":"2019","unstructured":"Souliotis VL, Vlachogiannis NI, Pappa M, Argyriou A, Sfikakis PP. DNA damage accumulation, defective chromatin organization and deficient DNA repair capacity in patients with rheumatoid arthritis. Clin Immunol. 2019;203:28\u201336.","journal-title":"Clin Immunol"},{"issue":"1","key":"1050_CR41","doi-asserted-by":"publisher","first-page":"2961","DOI":"10.1038\/s41467-022-30604-0","volume":"13","author":"A Cristini","year":"2022","unstructured":"Cristini A, Tellier M, Constantinescu F, Accalai C, Albulescu LO, Heiringhoff R, Bery N, Sordet O, Murphy S, Gromak N. RNase H2, mutated in Aicardi-Goutieres Syndrome, resolves co-transcriptional R-loops to prevent DNA breaks and inflammation. Nat Commun. 2022;13(1):2961.","journal-title":"Nat Commun"},{"issue":"24","key":"1050_CR42","doi-asserted-by":"publisher","first-page":"3897","DOI":"10.1016\/j.neuron.2021.11.019","volume":"109","author":"MF Lavin","year":"2021","unstructured":"Lavin MF, Yeo AJ. DNA damage rather than type I IFN signaling is the primary mediator of neural dysfunction in Aicardi-Goutieres Syndrome after RNASEH2 disruption. Neuron. 2021;109(24):3897\u2013900.","journal-title":"Neuron"},{"issue":"3","key":"1050_CR43","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204845","volume":"74","author":"S Kretschmer","year":"2015","unstructured":"Kretschmer S, Wolf C, Konig N, Staroske W, Guck J, Hausler M, Luksch H, Nguyen LA, Kim B, Alexopoulou D, et al. SAMHD1 prevents autoimmunity by maintaining genome stability. Ann Rheum Dis. 2015;74(3): e17.","journal-title":"Ann Rheum Dis"},{"issue":"1","key":"1050_CR44","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1084\/jem.20181505","volume":"216","author":"Z Chen","year":"2019","unstructured":"Chen Z, Amro EM, Becker F, Holzer M, Rasa SMM, Njeru SN, Han B, Di Sanzo S, Chen Y, Tang D, et al. Cohesin-mediated NF-kappaB signaling limits hematopoietic stem cell self-renewal in aging and inflammation. J Exp Med. 2019;216(1):152\u201375.","journal-title":"J Exp Med"},{"issue":"9","key":"1050_CR45","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1038\/s41590-018-0184-1","volume":"19","author":"S Cuartero","year":"2018","unstructured":"Cuartero S, Weiss FD, Dharmalingam G, Guo Y, Ing-Simmons E, Masella S, Robles-Rebollo I, Xiao X, Wang YF, Barozzi I, et al. Control of inducible gene expression links cohesin to hematopoietic progenitor self-renewal and differentiation. Nat Immunol. 2018;19(9):932\u201341.","journal-title":"Nat Immunol"},{"issue":"7253","key":"1050_CR46","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1038\/nature08079","volume":"460","author":"S Hadjur","year":"2009","unstructured":"Hadjur S, Williams LM, Ryan NK, Cobb BS, Sexton T, Fraser P, Fisher AG, Merkenschlager M. Cohesins form chromosomal cis-interactions at the developmentally regulated IFNG locus. Nature. 2009;460(7253):410\u20133.","journal-title":"Nature"},{"issue":"2","key":"1050_CR47","doi-asserted-by":"publisher","first-page":"999","DOI":"10.4049\/jimmunol.182.2.999","volume":"182","author":"C Ribeiro de Almeida","year":"2009","unstructured":"Ribeiro de Almeida C, Heath H, Krpic S, Dingjan GM, van Hamburg JP, Bergen I, van de Nobelen S, Sleutels F, Grosveld F, Galjart N, Hendriks RW. Critical role for the transcription regulator CCCTC-binding factor in the control of Th2 cytokine expression. J Immunol. 2009;182(2):999\u20131010.","journal-title":"J Immunol"},{"issue":"11","key":"1050_CR48","doi-asserted-by":"publisher","first-page":"12881","DOI":"10.1002\/cam4.5891","volume":"12","author":"J Li","year":"2023","unstructured":"Li J, Zhou Q, Liu L, He J. Effects of SMC1A on immune microenvironment and cancer stem cells in colon adenocarcinoma. Cancer Med. 2023;12(11):12881\u201395.","journal-title":"Cancer Med"},{"issue":"1","key":"1050_CR49","doi-asserted-by":"publisher","first-page":"4301","DOI":"10.1038\/s41467-022-31892-2","volume":"13","author":"J Minderjahn","year":"2022","unstructured":"Minderjahn J, Fischer A, Maier K, Mendes K, Nuetzel M, Raithel J, Stanewsky H, Ackermann U, Mansson R, Gebhard C, Rehli M. Postmitotic differentiation of human monocytes requires cohesin-structured chromatin. Nat Commun. 2022;13(1):4301.","journal-title":"Nat Commun"},{"issue":"1","key":"1050_CR50","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.1038\/s41467-018-03782-z","volume":"9","author":"S Ding","year":"2018","unstructured":"Ding S, Diep J, Feng N, Ren L, Li B, Ooi YS, Wang X, Brulois KF, Yasukawa LL, Li X, et al. STAG2 deficiency induces interferon responses via cGAS-STING pathway and restricts virus infection. Nat Commun. 2018;9(1):1485.","journal-title":"Nat Commun"},{"issue":"1","key":"1050_CR51","doi-asserted-by":"publisher","first-page":"4342","DOI":"10.1038\/s41467-022-31192-9","volume":"13","author":"I Robles-Rebollo","year":"2022","unstructured":"Robles-Rebollo I, Cuartero S, Canellas-Socias A, Wells S, Karimi MM, Mereu E, Chivu AG, Heyn H, Whilding C, Dormann D, et al. Cohesin couples transcriptional bursting probabilities of inducible enhancers and promoters. Nat Commun. 2022;13(1):4342.","journal-title":"Nat Commun"},{"issue":"8","key":"1050_CR52","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1038\/ng1845","volume":"38","author":"YJ Crow","year":"2006","unstructured":"Crow YJ, Hayward BE, Parmar R, Robins P, Leitch A, Ali M, Black DN, van Bokhoven H, Brunner HG, Hamel BC, et al. Mutations in the gene encoding the 3\u2019-5\u2019 DNA exonuclease TREX1 cause Aicardi-Goutieres Syndrome at the AGS1 locus. Nat Genet. 2006;38(8):917\u201320.","journal-title":"Nat Genet"},{"issue":"7","key":"1050_CR53","doi-asserted-by":"publisher","first-page":"107090","DOI":"10.1016\/j.isci.2023.107090","volume":"26","author":"H Du","year":"2023","unstructured":"Du H, Xiao N, Zhang S, Zhou X, Zhang Y, Lu Z, Fu Y, Huang M, Xu S, Chen Q. Suppression of TREX1 deficiency-induced cellular senescence and interferonopathies by inhibition of DNA damage response. iScience. 2023;26(7):107090.","journal-title":"iScience"},{"issue":"7","key":"1050_CR54","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1182\/blood-2013-04-490847","volume":"123","author":"R Clifford","year":"2014","unstructured":"Clifford R, Louis T, Robbe P, Ackroyd S, Burns A, Timbs AT, Wright Colopy G, Dreau H, Sigaux F, Judde JG, et al. SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage. Blood. 2014;123(7):1021\u201331.","journal-title":"Blood"},{"issue":"8","key":"1050_CR55","doi-asserted-by":"publisher","first-page":"1921","DOI":"10.1016\/j.celrep.2017.08.008","volume":"20","author":"W Daddacha","year":"2017","unstructured":"Daddacha W, Koyen AE, Bastien AJ, Head PE, Dhere VR, Nabeta GN, Connolly EC, Werner E, Madden MZ, Daly MB, et al. SAMHD1 promotes DNA end resection to facilitate DNA repair by homologous recombination. Cell Rep. 2017;20(8):1921\u201335.","journal-title":"Cell Rep"},{"key":"1050_CR56","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/j.molimm.2018.08.005","volume":"101","author":"A Martinez-Lopez","year":"2018","unstructured":"Martinez-Lopez A, Martin-Fernandez M, Buta S, Kim B, Bogunovic D, Diaz-Griffero F. SAMHD1 deficient human monocytes autonomously trigger type I interferon. Mol Immunol. 2018;101:450\u201360.","journal-title":"Mol Immunol"},{"issue":"7353","key":"1050_CR57","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1038\/nature10117","volume":"474","author":"N Laguette","year":"2011","unstructured":"Laguette N, Sobhian B, Casartelli N, Ringeard M, Chable-Bessia C, Segeral E, Yatim A, Emiliani S, Schwartz O, Benkirane M. SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx. Nature. 2011;474(7353):654\u20137.","journal-title":"Nature"},{"issue":"11","key":"1050_CR58","doi-asserted-by":"publisher","first-page":"1682","DOI":"10.1038\/nm.2964","volume":"18","author":"HM Baldauf","year":"2012","unstructured":"Baldauf HM, Pan X, Erikson E, Schmidt S, Daddacha W, Burggraf M, Schenkova K, Ambiel I, Wabnitz G, Gramberg T, et al. SAMHD1 restricts HIV-1 infection in resting CD4(+) T cells. Nat Med. 2012;18(11):1682\u20137.","journal-title":"Nat Med"},{"key":"1050_CR59","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1112761","volume":"14","author":"L Gutierrez-Chamorro","year":"2023","unstructured":"Gutierrez-Chamorro L, Felip E, Bernat-Peguera A, Ezeonwumelu IJ, Teruel I, Martinez-Cardus A, Clotet B, Riveira-Munoz E, Romeo M, Margeli M, Ballana E. SAMHD1 expression modulates innate immune activation and correlates with ovarian cancer prognosis. Front Immunol. 2023;14: 1112761.","journal-title":"Front Immunol"},{"issue":"6","key":"1050_CR60","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1038\/labinvest.2017.25","volume":"97","author":"R Sackstein","year":"2017","unstructured":"Sackstein R, Schatton T, Barthel SR. T-lymphocyte homing: an underappreciated yet critical hurdle for successful cancer immunotherapy. Lab Invest. 2017;97(6):669\u201397.","journal-title":"Lab Invest"},{"issue":"9","key":"1050_CR61","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1038\/ni.f.214","volume":"9","author":"F Sallusto","year":"2008","unstructured":"Sallusto F, Baggiolini M. Chemokines and leukocyte traffic. Nat Immunol. 2008;9(9):949\u201352.","journal-title":"Nat Immunol"},{"issue":"14","key":"1050_CR62","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1056\/NEJM200010053431407","volume":"343","author":"UH von Andrian","year":"2000","unstructured":"von Andrian UH, Mackay CR. T-cell function and migration. Two sides of the same coin. N Engl J Med. 2000;343(14):1020\u201334.","journal-title":"N Engl J Med"},{"key":"1050_CR63","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1146\/annurev-immunol-042617-053214","volume":"37","author":"D Masopust","year":"2019","unstructured":"Masopust D, Soerens AG. Tissue-resident T eells and other resident leukocytes. Annu Rev Immunol. 2019;37:521\u201346.","journal-title":"Annu Rev Immunol"},{"issue":"12","key":"1050_CR64","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1038\/s41584-019-0323-6","volume":"15","author":"Y Miyabe","year":"2019","unstructured":"Miyabe Y, Lian J, Miyabe C, Luster AD. Chemokines in rheumatic diseases: pathogenic role and therapeutic implications. Nat Rev Rheumatol. 2019;15(12):731\u201346.","journal-title":"Nat Rev Rheumatol"},{"issue":"7","key":"1050_CR65","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1038\/s41590-019-0398-x","volume":"20","author":"A Arazi","year":"2019","unstructured":"Arazi A, Rao DA, Berthier CC, Davidson A, Liu Y, Hoover PJ, Chicoine A, Eisenhaure TM, Jonsson AH, Li S, et al. The immune cell landscape in kidneys of patients with lupus nephritis. Nat Immunol. 2019;20(7):902\u201314.","journal-title":"Nat Immunol"},{"issue":"24","key":"1050_CR66","doi-asserted-by":"publisher","first-page":"3962","DOI":"10.1016\/j.neuron.2021.09.040","volume":"109","author":"Downing SM Aditi","year":"2021","unstructured":"Aditi Downing SM, Schreiner PA, Kwak YD, Li Y, Shaw TI, Russell HR, McKinnon PJ. Genome instability independent of type I interferon signaling drives neuropathology caused by impaired ribonucleotide excision repair. Neuron. 2021;109(24):3962-3979 e3966.","journal-title":"Neuron"},{"issue":"Pt 3","key":"1050_CR67","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1042\/BST0370535","volume":"37","author":"T Lindahl","year":"2009","unstructured":"Lindahl T, Barnes DE, Yang YG, Robins P. Biochemical properties of mammalian TREX1 and its association with DNA replication and inherited inflammatory disease. Biochem Soc Trans. 2009;37(Pt 3):535\u20138.","journal-title":"Biochem Soc Trans"},{"issue":"3","key":"1050_CR68","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1002\/jcp.25106","volume":"231","author":"G Fazio","year":"2016","unstructured":"Fazio G, Gaston-Massuet C, Bettini LR, Graziola F, Scagliotti V, Cereda A, Ferrari L, Mazzola M, Cazzaniga G, Giordano A, et al. CyclinD1 down-regulation and increased apoptosis are common features of cohesinopathies. J Cell Physiol. 2016;231(3):613\u201322.","journal-title":"J Cell Physiol"},{"issue":"34","key":"1050_CR69","doi-asserted-by":"publisher","first-page":"54370","DOI":"10.18632\/oncotarget.11029","volume":"7","author":"V Marcu-Malina","year":"2016","unstructured":"Marcu-Malina V, Goldberg S, Vax E, Amariglio N, Goldstein I, Rechavi G. ADAR1 is vital for B cell lineage development in the mouse bone marrow. Oncotarget. 2016;7(34):54370\u20139.","journal-title":"Oncotarget"},{"issue":"9","key":"1050_CR70","doi-asserted-by":"publisher","first-page":"eadk0820","DOI":"10.1126\/sciadv.adk0820","volume":"10","author":"D Luca","year":"2024","unstructured":"Luca D, Lee S, Hirota K, Okabe Y, Uehori J, Izawa K, Lanz AL, Schutte V, Sivri B, Tsukamoto Y, et al. Aberrant RNA sensing in regulatory T cells causes systemic autoimmunity. Sci Adv. 2024;10(9):eadk0820.","journal-title":"Sci Adv"},{"issue":"4","key":"1050_CR71","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/j.chom.2013.09.009","volume":"14","author":"A Sze","year":"2013","unstructured":"Sze A, Belgnaoui SM, Olagnier D, Lin R, Hiscott J, van Grevenynghe J. Host restriction factor SAMHD1 limits human T cell leukemia virus type 1 infection of monocytes via STING-mediated apoptosis. Cell Host Microbe. 2013;14(4):422\u201334.","journal-title":"Cell Host Microbe"}],"container-title":["Pediatric Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12969-024-01050-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12969-024-01050-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12969-024-01050-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T08:22:26Z","timestamp":1737966146000},"score":1,"resource":{"primary":{"URL":"https:\/\/ped-rheum.biomedcentral.com\/articles\/10.1186\/s12969-024-01050-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,27]]},"references-count":71,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["1050"],"URL":"https:\/\/doi.org\/10.1186\/s12969-024-01050-7","relation":{},"ISSN":["1546-0096"],"issn-type":[{"value":"1546-0096","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,27]]},"assertion":[{"value":"30 June 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 December 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 January 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The experimental protocol was established, according to the ethical guidelines of the Helsinki Declaration and was approved by the Human Ethics Committee of Attikon University Hospital, (Athens, Greece, protocol 10|22-6-2017). Written informed consent was obtained from all participants or their guardians.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Patients or guardian of patients gave informed consent for publishing the research results or images after anonymization.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors have no competing interests to declare that are relevant to the content of this article. The authors have no relevant financial or non\u2011financial interests to disclose.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"11"}}