Sökning: onr:"swepub:oai:gup.ub.gu.se/338274" > The Role of Interfe...
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000 | 07651naa a2201477 4500 | |
001 | oai:gup.ub.gu.se/338274 | |
003 | SwePub | |
008 | 240613s2024 | |||||||||||000 ||eng| | |
024 | 7 | a https://gup.ub.gu.se/publication/3382742 URI |
024 | 7 | a https://doi.org/10.1056/NEJMoa23126652 DOI |
040 | a (SwePub)gu | |
041 | a eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Oikonomou, Vasileios4 aut |
245 | 1 0 | a The Role of Interferon-γ in Autoimmune Polyendocrine Syndrome Type 1. |
264 | 1 | c 2024 |
520 | a Autoimmune polyendocrine syndrome type 1 (APS-1) is a life-threatening, autosomal recessive syndrome caused by autoimmune regulator (AIRE) deficiency. In APS-1, self-reactive T cells escape thymic negative selection, infiltrate organs, and drive autoimmune injury. The effector mechanisms governing T-cell-mediated damage in APS-1 remain poorly understood.We examined whether APS-1 could be classified as a disease mediated by interferon-γ. We first assessed patients with APS-1 who were participating in a prospective natural history study and evaluated mRNA and protein expression in blood and tissues. We then examined the pathogenic role of interferon-γ using Aire-/-Ifng-/- mice and Aire-/- mice treated with the Janus kinase (JAK) inhibitor ruxolitinib. On the basis of our findings, we used ruxolitinib to treat five patients with APS-1 and assessed clinical, immunologic, histologic, transcriptional, and autoantibody responses.Patients with APS-1 had enhanced interferon-γ responses in blood and in all examined autoimmunity-affected tissues. Aire-/- mice had selectively increased interferon-γ production by T cells and enhanced interferon-γ, phosphorylated signal transducer and activator of transcription 1 (pSTAT1), and CXCL9 signals in multiple organs. Ifng ablation or ruxolitinib-induced JAK-STAT blockade in Aire-/- mice normalized interferon-γ responses and averted T-cell infiltration and damage in organs. Ruxolitinib treatment of five patients with APS-1 led to decreased levels of T-cell-derived interferon-γ, normalized interferon-γ and CXCL9 levels, and remission of alopecia, oral candidiasis, nail dystrophy, gastritis, enteritis, arthritis, Sjögren's-like syndrome, urticaria, and thyroiditis. No serious adverse effects from ruxolitinib were identified in these patients.Our findings indicate that APS-1, which is caused by AIRE deficiency, is characterized by excessive, multiorgan interferon-γ-mediated responses. JAK inhibition with ruxolitinib in five patients showed promising results. (Funded by the National Institute of Allergy and Infectious Diseases and others.). | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Pediatrik0 (SwePub)302212 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Pediatrics0 (SwePub)302212 hsv//eng |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Immunologi inom det medicinska området0 (SwePub)301102 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Immunology in the medical area0 (SwePub)301102 hsv//eng |
653 | a Polyendocrinopathies | |
653 | a Autoimmune | |
653 | a genetics | |
653 | a drug therapy | |
653 | a immunology | |
653 | a Interferon-gamma | |
653 | a metabolism | |
653 | a genetics | |
653 | a Humans | |
653 | a Animals | |
653 | a Nitriles | |
653 | a therapeutic use | |
653 | a Mice | |
653 | a Pyrazoles | |
653 | a therapeutic use | |
653 | a pharmacology | |
653 | a Pyrimidines | |
653 | a therapeutic use | |
653 | a Transcription Factors | |
653 | a genetics | |
653 | a AIRE Protein | |
653 | a Female | |
653 | a Male | |
653 | a Mice | |
653 | a Knockout | |
653 | a Adult | |
653 | a Chemokine CXCL9 | |
653 | a genetics | |
653 | a Autoantibodies | |
653 | a blood | |
653 | a T-Lymphocytes | |
653 | a immunology | |
653 | a Janus Kinase Inhibitors | |
653 | a therapeutic use | |
700 | 1 | a Smith, Grace4 aut |
700 | 1 | a Constantine, Gregory M4 aut |
700 | 1 | a Schmitt, Monica M4 aut |
700 | 1 | a Ferré, Elise M N4 aut |
700 | 1 | a Alejo, Julie C4 aut |
700 | 1 | a Riley, Deanna4 aut |
700 | 1 | a Kumar, Dhaneshwar4 aut |
700 | 1 | a Dos Santos Dias, Lucas4 aut |
700 | 1 | a Pechacek, Joseph4 aut |
700 | 1 | a Hadjiyannis, Yannis4 aut |
700 | 1 | a Webb, Taura4 aut |
700 | 1 | a Seifert, Bryce A4 aut |
700 | 1 | a Ghosh, Rajarshi4 aut |
700 | 1 | a Walkiewicz, Magdalena4 aut |
700 | 1 | a Martin, Daniel4 aut |
700 | 1 | a Besnard, Marine4 aut |
700 | 1 | a Snarr, Brendan D4 aut |
700 | 1 | a Deljookorani, Shiva4 aut |
700 | 1 | a Lee, Chyi-Chia R4 aut |
700 | 1 | a DiMaggio, Tom4 aut |
700 | 1 | a Barber, Princess4 aut |
700 | 1 | a Rosen, Lindsey B4 aut |
700 | 1 | a Cheng, Aristine4 aut |
700 | 1 | a Rastegar, Andre4 aut |
700 | 1 | a de Jesus, Adriana A4 aut |
700 | 1 | a Stoddard, Jennifer4 aut |
700 | 1 | a Kuehn, Hye Sun4 aut |
700 | 1 | a Break, Timothy J4 aut |
700 | 1 | a Kong, Heidi H4 aut |
700 | 1 | a Castelo-Soccio, Leslie4 aut |
700 | 1 | a Colton, Ben4 aut |
700 | 1 | a Warner, Blake M4 aut |
700 | 1 | a Kleiner, David E4 aut |
700 | 1 | a Quezado, Martha M4 aut |
700 | 1 | a Davis, Jeremy L4 aut |
700 | 1 | a Fennelly, Kevin P4 aut |
700 | 1 | a Olivier, Kenneth N4 aut |
700 | 1 | a Rosenzweig, Sergio D4 aut |
700 | 1 | a Suffredini, Anthony F4 aut |
700 | 1 | a Anderson, Mark S4 aut |
700 | 1 | a Swidergall, Marc4 aut |
700 | 1 | a Guillonneau, Carole4 aut |
700 | 1 | a Notarangelo, Luigi D4 aut |
700 | 1 | a Goldbach-Mansky, Raphaela4 aut |
700 | 1 | a Neth, Olaf4 aut |
700 | 1 | a Monserrat-Garcia, Maria Teresa4 aut |
700 | 1 | a Valverde-Fernandez, Justo4 aut |
700 | 1 | a Lucena, Jose Manuel4 aut |
700 | 1 | a Gomez-Gila, Ana Lucia4 aut |
700 | 1 | a Garcia Rojas, Angela4 aut |
700 | 1 | a Seppänen, Mikko R J4 aut |
700 | 1 | a Lohi, Jouko4 aut |
700 | 1 | a Hero, Matti4 aut |
700 | 1 | a Laakso, Saila4 aut |
700 | 1 | a Klemetti, Paula4 aut |
700 | 1 | a Lundberg, Vanjau Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Clinical Sciences, Department of Pediatrics,Institute of Medicine, Department of Rheumatology and Inflammation Research4 aut0 (Swepub:gu)xlunva |
700 | 1 | a Ekwall, Olov,d 1968u Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Medicine, Department of Rheumatology and Inflammation Research,Institute of Clinical Sciences, Department of Pediatrics4 aut0 (Swepub:gu)xekwol |
700 | 1 | a Olbrich, Peter4 aut |
700 | 1 | a Winer, Karen K4 aut |
700 | 1 | a Afzali, Behdad4 aut |
700 | 1 | a Moutsopoulos, Niki M4 aut |
700 | 1 | a Holland, Steven M4 aut |
700 | 1 | a Heller, Theo4 aut |
700 | 1 | a Pittaluga, Stefania4 aut |
700 | 1 | a Lionakis, Michail S4 aut |
710 | 2 | a Göteborgs universitetb Institutionen för kliniska vetenskaper, Avdelningen för pediatrik4 org |
773 | 0 | t The New England journal of medicineg 390:20, s. 1873-1884q 390:20<1873-1884x 1533-4406 |
856 | 4 8 | u https://gup.ub.gu.se/publication/338274 |
856 | 4 8 | u https://doi.org/10.1056/NEJMoa2312665 |
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