title: Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease.
abstract: Monogenic causes of autoimmunity provide key insights into the complex regulation of the immune system. We report a new monogenic cause of autoimmunity resulting from de novo germline activating STAT3 mutations in five individuals with a spectrum of early-onset autoimmune disease, including type 1 diabetes. These findings emphasize the critical role of STAT3 in autoimmune disease and contrast with the germline inactivating STAT3 mutations that result in hyper IgE syndrome.
authors.affiliation: Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, EX2 5DW, UK.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Flanagan
authors.affiliation: Folkhälsan Institute of Genetics, University of Helsinki, Helsinki, Finland.|Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland.
authors.forename: Emma
authors.initials: E
authors.lastname: Haapaniemi
authors.affiliation: Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, EX2 5DW, UK.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Russell
authors.affiliation: Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, EX2 5DW, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Caswell
authors.affiliation: Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, EX2 5DW, UK.
authors.forename: Hana Lango
authors.initials: HL
authors.lastname: Allen
authors.affiliation: Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, EX2 5DW, UK.
authors.forename: Elisa
authors.initials: E
authors.lastname: De Franco
authors.affiliation: Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, EX2 5DW, UK.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: McDonald
authors.affiliation: Hematology Research Unit Helsinki, Department of Hematology, University of Helsinki.|Helsinki University Central Hospital Cancer Center, Helsinki, Finland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Rajala
authors.affiliation: Department of Clinical Sciences, Lund University, Lund, Sweden.|CRC, Skåne University Hospital SUS, Malmö, Sweden.
authors.forename: Anita
authors.initials: A
authors.lastname: Ramelius
authors.affiliation: Bristol Royal Hospital for Children, Upper Maudlin Street, Bristol, BS2 8BJ, UK.
authors.forename: John
authors.initials: J
authors.lastname: Barton
authors.affiliation: Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland.|Children's Hospital, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Kaarina
authors.initials: K
authors.lastname: Heiskanen
authors.affiliation: Department of Pediatrics, Kuopio University Hospital, Helsinki, Finland.
authors.forename: Tarja
authors.initials: T
authors.lastname: Heiskanen-Kosma
authors.affiliation: Children's Hospital, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Merja
authors.initials: M
authors.lastname: Kajosaari
authors.affiliation: Department of Diabetes and Endocrinology, Children's University Hospital, Temple St., Dublin 1, Ireland.
authors.forename: Nuala P
authors.initials: NP
authors.lastname: Murphy
authors.affiliation: Department of Endocrinology, Institute for Mother and Child Health Care of Serbia 'Dr Vukan Cupic', Belgrade, Serbia.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Milenkovic
authors.affiliation: Immunodeficiency Unit, Division of Infectious Diseases, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Seppänen
authors.affiliation: Department of Clinical Sciences, Lund University, Lund, Sweden.|CRC, Skåne University Hospital SUS, Malmö, Sweden.
authors.forename: Åke
authors.initials: Å
authors.lastname: Lernmark
authors.affiliation: Hematology Research Unit Helsinki, Department of Hematology, University of Helsinki.|Helsinki University Central Hospital Cancer Center, Helsinki, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Mustjoki
authors.affiliation: Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland.|Children's Hospital, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Otonkoski
authors.affiliation: Folkhälsan Institute of Genetics, University of Helsinki, Helsinki, Finland.|Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland.|Department of Biosciences and Nutrition, Karolinska Institutet, Hälsovägen 7, 14183 Huddinge, Sweden.|Center for Innovative Medicine, Karolinska Institutet, Hälsovägen 7, 14183 Huddinge, Sweden.
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
authors.affiliation: Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, EX2 5DW, UK.
authors.forename: Noel G
authors.initials: NG
authors.lastname: Morgan
authors.affiliation: Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, EX2 5DW, UK.
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.affiliation: Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, EX2 5DW, UK.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
mesh_terms: D000595:Amino Acid Sequence; D001327:Autoimmune Diseases / Q000235:genetics*; D002460:Cell Line; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D057809:HEK293 Cells; D006801:Humans; D007589:Job Syndrome / Q000235:genetics; D008969:Molecular Sequence Data; D050796:STAT3 Transcription Factor / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human