{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T20:39:42Z","timestamp":1793047182598,"version":"4.5.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2019,2,14]],"date-time":"2019-02-14T00:00:00Z","timestamp":1550102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"DOI":"10.3389\/fimmu.2019.00077","type":"journal-article","created":{"date-parts":[[2019,2,14]],"date-time":"2019-02-14T04:22:38Z","timestamp":1550118158000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Disseminated and Congenital Toxoplasmosis in a Mother and Child With Activated PI3-Kinase \u03b4 Syndrome Type 2 (APDS2): Case Report and a Literature Review of Toxoplasma Infections in Primary Immunodeficiencies"],"prefix":"10.3389","volume":"10","author":[{"given":"Djuro","family":"Karanovic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian C.","family":"Michelow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony R.","family":"Hayward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suk See","family":"DeRavin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ottavia M.","family":"Delmonte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Grigg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam Kerry","family":"Dobbs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie E.","family":"Niemela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Stoddard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaid","family":"Alhinai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Rybak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Hernandez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Pittaluga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio D.","family":"Rosenzweig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulbu","family":"Uzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi D.","family":"Notarangelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2019,2,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1038\/nri.2016.93","article-title":"PI3K\u03b4 and primary immunodeficiencies","volume":"16","author":"Lucas","year":"2016","journal-title":"Nat Rev Immunol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1126\/science.1243292","article-title":"Phosphoinositide 3-kinase delta gene mutation predisposes to respiratory infection and airway damage","volume":"342","author":"Angulo","year":"2013","journal-title":"Science"},{"key":"B3","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/ni.2771","article-title":"Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110delta result in T cell senescence and human immunodeficiency","volume":"15","author":"Lucas","year":"2014","journal-title":"Nat Immunol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.ajhg.2013.05.023","article-title":"SHORT syndrome with a partial lipodystrophy due to impaired phosphatidylinositol 3 kinase signaling","volume":"93","author":"Chudasama","year":"2013","journal-title":"Am J Hum Genet."},{"key":"B5","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.ajhg.2013.06.005","article-title":"Mutations in PIK3R1 cause SHORT syndrome","volume":"93","author":"Dyment","year":"2013","journal-title":"Am J Hum Genet."},{"key":"B6","doi-asserted-by":"publisher","first-page":"3923","DOI":"10.1172\/JCI75746","article-title":"A human immunodeficiency caused by mutations in the PIK3R1 gene","volume":"124","author":"Deau","year":"2014","journal-title":"J Clin Invest."},{"key":"B7","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.clim.2015.04.014","article-title":"Altered germinal center reaction and abnormal B cell peripheral maturation in PI3KR1-mutated patients presenting with HIGM-like phenotype","volume":"159","author":"Lougaris","year":"2015","journal-title":"Clin Immunol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/j.jaci.2016.06.021","article-title":"Clinical spectrum and features of activated phosphoinositide 3-kinase \u03b4 syndrome: a large patient cohort study","volume":"139","author":"Coulter","year":"2017","journal-title":"J Allergy Clin Immunol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.jaci.2016.03.022","article-title":"Clinical and immunologic phenotype associated with activated phosphoinositide 3-kinase \u03b4 syndrome 2: a cohort study","volume":"138","author":"Elkaim","year":"2016","journal-title":"J Allergy Clin Immunol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.clim.2017.03.004","article-title":"Mutations in PIK3R1 can lead to APDS2, SHORT syndrome or a combination of the two","volume":"179","author":"Bravo","year":"2017","journal-title":"Clin Immunol."},{"key":"B11","volume-title":"Red Journal 2018: Report of the Committee on Infectious Diseases.","author":"Kimberlin","year":"2018"},{"key":"B12","doi-asserted-by":"publisher","first-page":"3090","DOI":"10.1128\/IAI.01722-14","article-title":"Complex immune cell interplay in the gamma interferon response during Toxoplasma gondii infection","volume":"82","author":"Sturge","year":"2014","journal-title":"Infect Immun."},{"key":"B13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/CBO9780511527005.003","article-title":"Biology of toxoplasmosis","volume-title":"Toxoplasmosis","author":"Peterson","year":"2001"},{"key":"B14","doi-asserted-by":"publisher","first-page":"6115","DOI":"10.1073\/pnas.90.13.6115","article-title":"Interleukin 12 is required for the T-lymphocyte-independent induction of interferon \u03b3 by an intracellular parasite and induces reisistance in T-cell-deficient hosts","volume":"90","author":"Gazzinelli","year":"1993","journal-title":"Proc Natl Acad Sci USA."},{"key":"B15","doi-asserted-by":"publisher","first-page":"31","DOI":"10.4049\/jimmunol.177.1.31","article-title":"Cutting edge: dendritic cells are essential for in vivo IL-12 production and development of resistance against Toxoplasma gondii infection in mice","volume":"177","author":"Liu","year":"2006","journal-title":"J Immunol."},{"key":"B16","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1084\/jem.186.11.1819","article-title":"In vivo microbial stimulation induces rapid CD40 ligand-independent production of interleukin 12 by dendritic cells and their redistribution to T cell areas","volume":"186","author":"Reis","year":"1997","journal-title":"J Exp Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1038\/76957","article-title":"CCR5 provides a signal for microbial induced production of IL-12 for CD8\u03b1+ dendritic cells","volume":"1","author":"Aliberti","year":"2000","journal-title":"Nat Immunol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1093\/intimm\/dxg108","article-title":"TLR2 as an essential molecule for protective immunity against Toxoplasma gondii infection","volume":"15","author":"Mun","year":"2003","journal-title":"Int Immunol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1626","DOI":"10.1126\/science.1109893","article-title":"TLR11 activation of dendritic cells by a protozoan profilin-like protein","volume":"308","author":"Yarovinsky","year":"2005","journal-title":"Science"},{"key":"B20","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1128\/IAI.62.5.1639-1642.1994","article-title":"Interleukin-12 enhances murine survival against acute toxoplasmosis","volume":"62","author":"Khan","year":"1994","journal-title":"Infect Immun."},{"key":"B21","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1084\/jem.158.3.670","article-title":"Identification of interferon-\u03b3 as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity","volume":"158","author":"Nathan","year":"1983","journal-title":"J Exp Med."},{"key":"B22","doi-asserted-by":"crossref","first-page":"286","DOI":"10.4049\/jimmunol.146.1.286","article-title":"Synergistic role of CD4+ and CD8+ T lymphocytes in IFN-\u03b3 production and protective immunity induced by an attenuated Toxoplasma gondii vaccine","volume":"146","author":"Gazzinelli","year":"1991","journal-title":"J Immunol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1023\/A:1027337923709","article-title":"Central nervous system toxoplasmosis with an increased proportion of circulating \u03b3\u03b4 t cells in a patient with hyper-IgM syndrome","volume":"18","author":"Leiva","year":"1998","journal-title":"J Clin Immunol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1136\/jcp.2008.058362","article-title":"Cerebral toxoplasmosis in a middle-aged man as first presentation of primary immunodeficiency due to a hypomorphic mutation in the CD40 ligand gene","volume":"61","author":"Yong","year":"2008","journal-title":"J Clin Pathol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"e8989","DOI":"10.1097\/MD.0000000000008989","article-title":"A delayed diagnosis of X-linked hyper IgM syndrome complicated with toxoplasmic encephalitis in a child","volume":"96","author":"Liu","year":"2017","journal-title":"Medicine"},{"key":"B26","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1007\/s004310050925","article-title":"Necrotizing toxoplasmic encephalitis in a child with the X-linked hyper-IgM syndrome","volume":"157","author":"Tsuge","year":"1998","journal-title":"Eur J Pediatr."},{"key":"B27","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/S0022-3476(97)70123-9","article-title":"Clinical spectrum of X-linked hyper-IgM syndrome","volume":"131","author":"Levy","year":"1997","journal-title":"J Pediatr."},{"key":"B28","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.clim.2017.09.011","article-title":"Severe Toxoplasma gondii infection in a member of a NFKB2-deficient family with T and B cell dysfunction","volume":"183","author":"Maccari","year":"2017","journal-title":"Clin Immunol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1097\/MD.0b013e3181fdd832","article-title":"Revisiting human IL-12R\u03b21 deficiency: a survey of 141 patients from 30 countries","volume":"89","author":"De Beaucoudrey","year":"2010","journal-title":"Medicine"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1093\/hmg\/ddr029","article-title":"Partial recessive IFN-\u03b3R1 deficiency: genetic, immunological and clinical features of 14 patients with 11 kindreds","volume":"20","author":"Sologuren","year":"2011","journal-title":"Human Mol Genet."},{"key":"B31","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1093\/cid\/civ1220","article-title":"Progressive multifocal leukoencephalopathy in primary immune deficiencies: STAT1 gain of function and review of the literature","volume":"62","author":"Zerbe","year":"2016","journal-title":"Clin Infect Dis."},{"key":"B32","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1007\/s10875-015-0161-5","article-title":"Late-onset disseminated Mycobacterium avium intracellulare complex infection (MAC), cerebral toxoplasmosis and salmonella sepsis in a German caucasian patient with unusual anti-interferon-gamma IgG1 autoantibodies","volume":"35","author":"Hanitsh","year":"2015","journal-title":"J Clin Immunol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.1136\/bjo.2005.078097","article-title":"Unilateral necrotizing toxoplasmic retinochoroiditis as the main clinical manifestation of a peptide transporter (TAP) deficiency","volume":"89","author":"Parissiadis","year":"2005","journal-title":"Br J Ophthalmol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.parint.2006.02.003","article-title":"A novel mutation for TAP deficiency and its possible association with Toxoplasmosis","volume":"55","author":"Dogu","year":"2006","journal-title":"Parasitol Int."},{"key":"B35","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1097\/00000441-198405000-00012","article-title":"Toxoplasmosis in a patient with common variable immunodeficiency","volume":"287","author":"Shachor","year":"1984","journal-title":"Am J Med Sci."},{"key":"B36","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1086\/517027","article-title":"Progressive multifocal leukoenceophalopathy in a patient with common variable immunodeficiency","volume":"26","author":"Scotton","year":"1998","journal-title":"Clin Infect Dis."},{"key":"B37","doi-asserted-by":"publisher","first-page":"2192","DOI":"10.1212\/01.WNL.0000145833.69409.2B","article-title":"Cerebral toxoplasmosis in a patient with common variable immunodeficiency","volume":"63","author":"Holtkamp","year":"2004","journal-title":"Neurology"},{"key":"B38","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1155\/2008\/614279","article-title":"Case report and review of the literature: Toxoplasma gondii encephalitis in a 40-year-old woman with common variable immunodeficiency and a new diagnosis of large granular lymphocytic leukemia","volume":"19","author":"Hofmann","year":"2008","journal-title":"Can J Infect Dis Med Microbiol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1186\/s12879-016-1801-y","article-title":"Cerebral toxoplasmosis in a patient with myasthenia gravis and thymoma with immunodeficiency\/Good's syndrome: a case report","volume":"16","author":"Sasson","year":"2016","journal-title":"BMC Infect Dis."},{"key":"B40","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.revmed.2016.08.005","article-title":"Good's syndrome and congential toxoplasmosis due to maternal reactivation during pregnancy","volume":"38","author":"Tahiria","year":"2017","journal-title":"Rev Med Interne"},{"key":"B41","doi-asserted-by":"publisher","first-page":"2686","DOI":"10.1128\/JCM.01077-13","article-title":"Atypical strain of Toxoplasma gondii causing fatal reactivation after hematopoietic stem cell transplantation in a patient with an underlying immunological deficiency","volume":"51","author":"Stajner","year":"2013","journal-title":"J Clin Microbiol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"35","DOI":"10.15406\/unoaj.2018.06.00200","article-title":"A case of Omenn syndrome accompanied by bilateral cystine stones: case report","volume":"6","author":"Cansever","year":"2018","journal-title":"Urol Nephrol Open Access J."},{"key":"B43","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1182\/blood.V85.4.1053.bloodjournal8541053","article-title":"A primary T-cell immunodeficiency associated with defective transmembrane calcium influx","volume":"85","author":"Le Deist","year":"1995","journal-title":"Blood"},{"key":"B44","doi-asserted-by":"publisher","first-page":"671","DOI":"10.4049\/jimmunol.178.2.671","article-title":"A costimulatory function for T cell CD40","volume":"178","author":"Munroe","year":"2007","journal-title":"J Immunol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"5258","DOI":"10.1128\/MCB.15.10.5258","article-title":"Regulation of interleukin 12 p40 expression through an NF-kappa B half-site","volume":"15","author":"Murphy","year":"1995","journal-title":"Mol Cell Biol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1084\/jem.175.3.683","article-title":"Polymorphisms in the tumor necrosis factor \u03b1 (TNF-\u03b1) gene correlate with murine resistance of development of toxoplasmic encephalitis and with levels of TNF-\u03b1 mRNA in infected brain tissue","volume":"175","author":"Freund","year":"1992","journal-title":"J Exp Med."},{"key":"B47","doi-asserted-by":"publisher","first-page":"3900","DOI":"10.4049\/jimmunol.169.7.3900","article-title":"Divergent role for TNF-\u03b1 in IFN-\u03b3-induced killing of Toxoplasma gondii and Salmonella typhimurium contributes to selective suscceptibility of patients with partial IFN-\u03b3 receptor 1 deficiency","volume":"169","author":"Jannsen","year":"2002","journal-title":"J Immunol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1530","DOI":"10.1056\/NEJMc051556","article-title":"Infliximab and reactivation of cerebral toxoplasmosis","volume":"353","author":"Young","year":"2005","journal-title":"N Eng J Med."},{"key":"B49","doi-asserted-by":"publisher","first-page":"2591","DOI":"10.1084\/jem.20070634","article-title":"TAP-1 indirectly regulates CD4+ T cell priming in Toxoplasma gondii infection by controlling NK cell IFN-gamma production","volume":"204","author":"Goldszmid","year":"2007","journal-title":"J Exp Med."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1086\/317471","article-title":"Toxoplasmosis after hematopoietic stem cell transplantation","volume":"31","author":"Martino","year":"2000","journal-title":"Clin Infect Dis."},{"key":"B51","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1086\/426447","article-title":"Early detection of Toxoplasma gondii infectiuon by molecular monitoring of Toxoplasma gondii in peripheral blood samples after allogeneic stem cell transplantation","volume":"40","author":"Martino","year":"2005","journal-title":"Clin Infect Dis."},{"key":"B52","doi-asserted-by":"publisher","first-page":"e66306","DOI":"10.1371\/journal.pone.0066306","article-title":"Toxoplasma gondii proliferation require down-regulation of host Nox-4 expression via activation of PI3 kinase\/Akt signaling pathway","volume":"8","author":"Zhou","year":"2013","journal-title":"PLoS ONE"},{"key":"B53","doi-asserted-by":"publisher","first-page":"6361","DOI":"10.1038\/s41598-017-06610-4","article-title":"NADPH oxidase 4 is required for the generation of macrophage migration inhibitory factor and host defense against Toxoplasma gondii infection","volume":"7","author":"Kim","year":"2017","journal-title":"Sci Rep."}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2019.00077\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T16:37:15Z","timestamp":1694623035000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2019.00077\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,14]]},"references-count":53,"alternative-id":["10.3389\/fimmu.2019.00077"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2019.00077","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,14]]},"article-number":"77"}}