{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:28:50Z","timestamp":1791419330653,"version":"4.3.3"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T00:00:00Z","timestamp":1598572800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Adenosine deaminase 2 deficiency (DADA2) is an autoinflammatory disease characterized by inflammatory vasculopathy, early strokes associated often with hypogammaglobulinemia. Pure red cell aplasia, thrombocytopenia, and neutropenia have been reported. The defect is due to biallelic loss of function of\n                    <jats:italic>ADA2<\/jats:italic>\n                    gene, coding for a protein known to regulate the catabolism of extracellular adenosine. We therefore investigated immune phenotype and B\u2010 and T\u2010cell responses in 14 DADA2 patients to address if\n                    <jats:italic>ADA2<\/jats:italic>\n                    mutation affects B\u2010 and T\u2010cell function.\n                  <\/jats:p>\n                  <jats:p>\n                    Here, we show a significant decrease in memory B\u00a0cells, in particular class switch memory, and an expansion of CD21\n                    <jats:sup>low<\/jats:sup>\n                    B\u00a0cells in DADA2 patients. In vitro stimulated B lymphocytes were able to secrete nonfunctional ADA2 protein, suggesting a cell intrinsic defect resulting in an impairment of B\u2010cell proliferation and differentiation. Moreover, CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u00a0cells were diminished; however, the frequency of circulating T follicular helper cells was significantly increased but they had an impairment in IL\u201021 production possibly contributing to an impaired B\u00a0cell help. Our findings suggest that\n                    <jats:italic>ADA2<\/jats:italic>\n                    mutation could lead to a B\u2010cell intrinsic defect but also to a defective Tfh cell function, which could contribute to the immunodeficient phenotype reported in DADA2 patients.\n                  <\/jats:p>","DOI":"10.1002\/eji.202048549","type":"journal-article","created":{"date-parts":[[2020,7,24]],"date-time":"2020-07-24T18:54:27Z","timestamp":1595616867000},"page":"206-219","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Dysregulation in B\u2010cell responses and T follicular helper cell function in ADA2 deficiency patients"],"prefix":"10.1002","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5868-7699","authenticated-orcid":false,"given":"Francesca","family":"Schena","sequence":"first","affiliation":[{"name":"Unit\u00e0 Operativa Semplice Dipartimentale Centro Malattie Autoinfiammatorie e Immunodeficienze IRCCS Istituto Giannina Gaslini  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Penco","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa Semplice Dipartimentale Centro Malattie Autoinfiammatorie e Immunodeficienze IRCCS Istituto Giannina Gaslini  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Volpi","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa Semplice Dipartimentale Centro Malattie Autoinfiammatorie e Immunodeficienze IRCCS Istituto Giannina Gaslini  Genova Italy"},{"name":"Dipartimento di Neuroscienze, riabilitazione, oftalmologia, genetica e scienze materno\u2010infantili (DINOGMI) Universit\u00e0 degli studi di Genova  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Pastorino","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa Semplice Dipartimentale Centro Malattie Autoinfiammatorie e Immunodeficienze IRCCS Istituto Giannina Gaslini  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Caorsi","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa Clinica Pediatrica e Reumatologia IRCCS Istituto Giannina Gaslini  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Kalli","sequence":"additional","affiliation":[{"name":"Center of Excellence for Biomedical Research\/Department of Internal Medicine Universit\u00e0 di Genova  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Fenoglio","sequence":"additional","affiliation":[{"name":"Center of Excellence for Biomedical Research\/Department of Internal Medicine Universit\u00e0 di Genova  Genova Italy"},{"name":"Ospedale Policlinico San Martino  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Salis","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Center of Excellence for Biomedical Research Universit\u00e0 di Genova  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arinna","family":"Bertoni","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa Semplice Dipartimentale Centro Malattie Autoinfiammatorie e Immunodeficienze IRCCS Istituto Giannina Gaslini  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignazia","family":"Prigione","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa Semplice Dipartimentale Centro Malattie Autoinfiammatorie e Immunodeficienze IRCCS Istituto Giannina Gaslini  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Bocca","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa Semplice Dipartimentale Centro Malattie Autoinfiammatorie e Immunodeficienze IRCCS Istituto Giannina Gaslini  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Insalaco","sequence":"additional","affiliation":[{"name":"Division of Rheumatology Department of Pediatric Medicine IRCCS Bambino Ges\u00f9 Children's Hospital  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"De Benedetti","sequence":"additional","affiliation":[{"name":"Division of Rheumatology Department of Pediatric Medicine IRCCS Bambino Ges\u00f9 Children's Hospital  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Antonini","sequence":"additional","affiliation":[{"name":"Core Facilities Flow\u2010Cytometry and Cell Imaging Laboratory IRCCS Istituto Giannina Gaslini  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Grossi","sequence":"additional","affiliation":[{"name":"UOSD Laboratory of Genetics and Genomics of Rare Diseases IRCCS Istituto Giannina Gaslini  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Signa","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa Semplice Dipartimentale Centro Malattie Autoinfiammatorie e Immunodeficienze IRCCS Istituto Giannina Gaslini  Genova Italy"},{"name":"Dipartimento di Neuroscienze, riabilitazione, oftalmologia, genetica e scienze materno\u2010infantili (DINOGMI) Universit\u00e0 degli studi di Genova  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Damonte","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Center of Excellence for Biomedical Research Universit\u00e0 di Genova  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Ceccherini","sequence":"additional","affiliation":[{"name":"UOSD Laboratory of Genetics and Genomics of Rare Diseases IRCCS Istituto Giannina Gaslini  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilberto","family":"Filaci","sequence":"additional","affiliation":[{"name":"Center of Excellence for Biomedical Research\/Department of Internal Medicine Universit\u00e0 di Genova  Genova Italy"},{"name":"Biotherapy Unit IRCCS Ospedale Policlinico San Martino  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Traggiai","sequence":"additional","affiliation":[{"name":"Novartis Institutes for Biomedical Research  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Gattorno","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa Semplice Dipartimentale Centro Malattie Autoinfiammatorie e Immunodeficienze IRCCS Istituto Giannina Gaslini  Genova Italy"},{"name":"Unit\u00e0 Operativa Clinica Pediatrica e Reumatologia IRCCS Istituto Giannina Gaslini  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1307361"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1307362"},{"key":"e_1_2_7_4_1","article-title":"Adenosine deaminase 2 deficiency","author":"Aksentijevich I.","journal-title":"GeneReviews\u00ae [Internet]. 2019 Aug 8. Seattle (WA): University of Washington, Seattle; 1993\u20132020."},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000669"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40147"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12969-016-0111-7"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.26912"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2016.06.058"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.01.012"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.03.016"},{"key":"e_1_2_7_12_1","first-page":"142","article-title":"ADA2 deficiency mimicking idiopathic multicentric Castleman disease","author":"Van Nieuwenhove E.","year":"2018","journal-title":"Pediatrics"},{"key":"e_1_2_7_13_1","first-page":"1","article-title":"ADA2 deficiency (DADA2) as an unrecognised cause of early onset polyarteritis nodosa and stroke: a multicentre national study","volume":"0","author":"Caorsi R.","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13302"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3693"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20050683"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.05.022"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1109764"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-016-2357-0"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13052-015-0184-9"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0901984106"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2010.12.001"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-04-345579"},{"key":"e_1_2_7_24_1","first-page":"440","article-title":"Altered expression of CD39 on memory regulatory T\u00a0cells in type 1 diabetes patients","volume":"11","author":"Zhang C.","year":"2018","journal-title":"J. Diabetes"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.13598"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201646574"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.12.012"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3153"},{"key":"e_1_2_7_29_1","first-page":"480","article-title":"Mutant ADA2 in vasculopathies","volume":"31","author":"Van Eyck L.","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.10.010"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39699"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.150024"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kev439"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201970107"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200535744"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2007-0528"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-931-0_10"}],"container-title":["European Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Feji.202048549","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.202048549","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/eji.202048549","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.202048549","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T12:39:53Z","timestamp":1693658393000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/eji.202048549"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,28]]},"references-count":36,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1002\/eji.202048549"],"URL":"https:\/\/doi.org\/10.1002\/eji.202048549","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/EJI.202048549\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.202048549\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.202048549\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.202048549\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.202048549\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.202048549\/v1\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.202048549\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.202048549\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.202048549\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.202048549\/v2\/response1","asserted-by":"object"}]},"ISSN":["0014-2980","1521-4141"],"issn-type":[{"value":"0014-2980","type":"print"},{"value":"1521-4141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,28]]},"assertion":[{"value":"2020-06-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}