{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:56:45Z","timestamp":1753891005990,"version":"3.41.2"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T00:00:00Z","timestamp":1672790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004329","name":"Javna Agencija za Raziskovalno Dejavnost RS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Aicardi\u2013Gouti\u00e8res syndrome (AGS) is a genetically determined early-onset progressive encephalopathy caused by mutations leading to overexpression of type I interferon (IFN) and resulting in various clinical phenotypes. A gain-of-function (GOF) mutation in the <jats:italic>IFIH1<\/jats:italic> gene is associated with robust production of type I IFN and activation of the Janus kinase (JAK) signal transducer and activator of the transcription (STAT) pathway, which can cause AGS type 7. We detail the clinical case of an infant who initially presented with <jats:italic>Pneumocystis jirovecii<\/jats:italic> pneumonia (PCP), had recurrent respiratory infections, and was later treated with a JAK inhibitor, baricitinib, because of a genetically confirmed GOF mutation in the <jats:italic>IFIH1<\/jats:italic> gene. This spectrum of <jats:italic>IFIH1<\/jats:italic> GOF mutations with overlapping features of hyperinflammation and severe opportunistic infection, which mimics combined immunodeficiency (CID), has not been described before. In this case, therapy with baricitinib effectively blocked IFN-\u03b1 activation and reduced STAT1 signaling but had no effect on the progression of the neurological disease.<\/jats:p>","DOI":"10.3389\/fimmu.2022.1033513","type":"journal-article","created":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T16:04:37Z","timestamp":1672848277000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Case report: Pneumocystis jirovecii pneumonia in a severe case of Aicardi\u2013Gouti\u00e8res syndrome with an IFIH1 gain-of-function mutation mimicking combined immunodeficiency"],"prefix":"10.3389","volume":"13","author":[{"given":"Mojca","family":"\u017deleznik","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aneta","family":"Soltirovska \u0160alamon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maru\u0161a","family":"Debeljak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ale\u0161","family":"Goropev\u0161ek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nata\u0161a","family":"\u0160u\u0161tar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Damjana","family":"Klju\u010dev\u0161ek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alojz","family":"Ihan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadej","family":"Av\u010din","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1002\/ana.410150109","article-title":"A progressive familial encephalopathy in infancy with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis","volume":"15","author":"Aicardi","year":"1984","journal-title":"Ann Neurol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.06.007","article-title":"Aicardi-gouti\u00e8res syndrome is caused by IFIH1 mutations","volume":"95","author":"Oda","year":"2014","journal-title":"Am J Hum Genet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1055\/s-0034-1389161","article-title":"Mutations in ADAR1 , IFIH1 , and RNASEH2B presenting as spastic paraplegia","volume":"45","author":"Crow","year":"2014","journal-title":"Neuropediatrics"},{"key":"B4","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1002\/ajmg.a.36887","article-title":"Characterization of human disease phenotypes associated with mutations in TREX1 , RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1. 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