{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T17:30:28Z","timestamp":1789579828789,"version":"build-2803163510"},"reference-count":9,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T00:00:00Z","timestamp":1676937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012680","name":"Universit\u00e4tsklinikum Hamburg-Eppendorf","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012680","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Autosomal dominant mutations in the C-terminal part of <jats:italic>TREX1<\/jats:italic> (pVAL235Glyfs<jats:sup>*<\/jats:sup>6) result in fatal retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCLS) without any treatment options. Here, we report on a treatment of a RVCLS patient with anti-retroviral drugs and the janus kinase (JAK) inhibitor ruxolitinib.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We collected clinical data of an extended family with RVCLS (<jats:italic>TREX1<\/jats:italic> pVAL235Glyfs<jats:sup>*<\/jats:sup>6). Within this family we identified a 45-year-old woman as index patient that we treated experimentally for 5 years and prospectively collected clinical, laboratory and imaging data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We report clinical details from 29 family members with 17 of them showing RVCLS symptoms. Treatment of the index patient with ruxolitinib for &amp;gt;4 years was well-tolerated and clinically stabilized RVCLS activity. Moreover, we noticed normalization of initially elevated <jats:italic>CXCL10<\/jats:italic> mRNA in peripheral blood monocular cells (PBMCs) and a reduction of antinuclear autoantibodies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>We provide evidence that JAK inhibition as RVCLS treatment appears safe and could slow clinical worsening in symptomatic adults. These results encourage further use of JAK inhibitors in affected individuals together with monitoring of <jats:italic>CXCL10<\/jats:italic> transcripts in PBMCs as useful biomarker of disease activity.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2023.1118369","type":"journal-article","created":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T05:44:35Z","timestamp":1676958275000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Case report: JAK inhibition as promising treatment option of fatal RVCLS due to TREX1 mutation (pVAL235Glyfs*6)"],"prefix":"10.3389","volume":"14","author":[{"given":"Friederike","family":"Ufer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne M.","family":"Ziegler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Altfeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel A.","family":"Friese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/j.immuni.2015.07.022","article-title":"Cytosolic nuclease TREX1 regulates oligosaccharyltransferase activity independent of nuclease activity to suppress immune activation","volume":"43","author":"Hasan","year":"2015","journal-title":"Immunity."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.1038\/ng2082","article-title":"C-terminal truncations in human 3'-5' DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy","volume":"39","author":"Richards","year":"2007","journal-title":"Nat Genet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1038\/nri3850","article-title":"Aicardi-Goutieres syndrome and the type I interferonopathies","volume":"15","author":"Crow","year":"2015","journal-title":"Nat Rev Immunol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.jaut.2017.03.001","article-title":"DNase-active TREX1 frame-shift mutants induce serologic autoimmunity in mice","volume":"81","author":"Sakai","year":"2017","journal-title":"J Autoimmun."},{"key":"B5","doi-asserted-by":"publisher","first-page":"3856","DOI":"10.1002\/art.37691","article-title":"Regulation of inflammatory responses in tumor necrosis factor-activated and rheumatoid arthritis synovial macrophages by JAK inhibitors","volume":"64","author":"Yarilina","year":"2012","journal-title":"Arthritis Rheum."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2909","DOI":"10.1093\/brain\/aww253","article-title":"Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations","volume":"139","author":"de Boer","year":"2016","journal-title":"Brain."},{"key":"B7","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/j.cell.2008.06.032","article-title":"Trex1 prevents cell-intrinsic initiation of autoimmunity","volume":"134","author":"Stetson","year":"2008","journal-title":"Cell."},{"key":"B8","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1038\/nrd.2017.201","article-title":"inhibition as a therapeutic strategy for immune and inflammatory diseases","volume":"17","author":"Schwartz","year":"2017","journal-title":"Nat Rev Drug Discov."},{"key":"B9","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1007\/s10456-017-9561-x","article-title":"CXCL10 suppression of hem- and lymph-angiogenesis in inflamed corneas through MMP13","volume":"20","author":"Gao","year":"2017","journal-title":"Angiogenesis."}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2023.1118369\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T05:44:38Z","timestamp":1676958278000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2023.1118369\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,21]]},"references-count":9,"alternative-id":["10.3389\/fneur.2023.1118369"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2023.1118369","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,21]]},"article-number":"1118369"}}