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dc.contributor.author
König, Nadja
dc.contributor.author
Fiehn, Christoph
dc.contributor.author
Wolf, Christine
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Schuster, Max
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Cura Costa, Emanuel
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Tüngler, Victoria
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Alvarez, Hugo Ariel
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Chara, Osvaldo
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Engel, Kerstin
dc.contributor.author
Goldbach Mansky, Raphaela
dc.contributor.author
Günther, Claudia
dc.contributor.author
Lee Kirsch, Min Ae
dc.date.available
2018-07-13T13:48:38Z
dc.date.issued
2017-02
dc.identifier.citation
König, Nadja; Fiehn, Christoph; Wolf, Christine; Schuster, Max; Cura Costa, Emanuel; et al.; Familial chilblain lupus due to a gain-of-function mutation in STING; B M J Publishing Group; Annals Of The Rheumatic Diseases; 76; 2; 2-2017; 468-472
dc.identifier.issn
0003-4967
dc.identifier.uri
http://hdl.handle.net/11336/51987
dc.description.abstract
Objectives Familial chilblain lupus is a monogenic form of cutaneous lupus erythematosus caused by loss-of-function mutations in the nucleases TREX1 or SAMHD1. In a family without TREX1 or SAMHD1 mutation, we sought to determine the causative gene and the underlying disease pathology. Methods Exome sequencing was used for disease gene identification. Structural analysis was performed by homology modelling and docking simulations. Type I interferon (IFN) activation was assessed in cells transfected with STING cDNA using an IFN-â reporter and Western blotting. IFN signatures in patient blood in response to tofacitinib treatment were measured by RT-PCR of IFN-stimulated genes. Results In a multigenerational family with five members affected with chilblain lupus, we identified a heterozygous mutation of STING, a signalling molecule in the cytosolic DNA sensing pathway. Structural and functional analyses indicate that mutant STING enhances homodimerisation in the absence of its ligand cGAMP resulting in constitutive type I IFN activation. Treatment of two affected family members with the Janus kinase ( JAK) inhibitor tofacitinib led to a marked suppression of the IFN signature. Conclusions A heterozygous gain-of-function mutation in STING can cause familial chilblain lupus. These findings expand the genetic spectrum of type I IFNdependent disorders and suggest that JAK inhibition may be of therapeutic value.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
B M J Publishing Group
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Sting
dc.subject
Familial Chilblain Lupus
dc.subject.classification
Medicina Critica y de Emergencia
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Medicina Clínica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Familial chilblain lupus due to a gain-of-function mutation in STING
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-06-08T14:27:13Z
dc.journal.volume
76
dc.journal.number
2
dc.journal.pagination
468-472
dc.journal.pais
Reino Unido
dc.journal.ciudad
Londres
dc.description.fil
Fil: König, Nadja. Technische Universität Dresden; Alemania
dc.description.fil
Fil: Fiehn, Christoph. Acura Akutklinik Für Rheumatologie Baden-baden; Alemania
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Fil: Wolf, Christine. Technische Universität Dresden; Alemania
dc.description.fil
Fil: Schuster, Max. Technische Universität Dresden; Alemania
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Fil: Cura Costa, Emanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; Argentina
dc.description.fil
Fil: Tüngler, Victoria. Technische Universität Dresden; Alemania
dc.description.fil
Fil: Alvarez, Hugo Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; Argentina
dc.description.fil
Fil: Chara, Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; Argentina
dc.description.fil
Fil: Engel, Kerstin. Technische Universität Dresden; Alemania
dc.description.fil
Fil: Goldbach Mansky, Raphaela. Technische Universität Dresden; Alemania
dc.description.fil
Fil: Günther, Claudia. National Institutes of Health; Estados Unidos
dc.description.fil
Fil: Lee Kirsch, Min Ae. Technische Universität Dresden; Alemania
dc.journal.title
Annals Of The Rheumatic Diseases
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://ard.bmj.com/content/76/2/468
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1136/annrheumdis-2016-209841


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