title: Autoantibodies Targeting a Collecting Duct-Specific Water Channel in Tubulointerstitial Nephritis.
abstract: Tubulointerstitial nephritis is a common cause of kidney failure and may have diverse etiologies. This form of nephritis is sometimes associated with autoimmune disease, but the role of autoimmune mechanisms in disease development is not well understood. Here, we present the cases of three patients with autoimmune polyendocrine syndrome type 1 who developed tubulointerstitial nephritis and ESRD in association with autoantibodies against kidney collecting duct cells. One of the patients developed autoantibodies targeting the collecting duct-specific water channel aquaporin 2, whereas autoantibodies of the two other patients reacted against the HOXB7 or NFAT5 transcription factors, which regulate the aquaporin 2 promoter. Our findings suggest that tubulointerstitial nephritis developed in these patients as a result of an autoimmune insult on the kidney collecting duct cells.
authors.affiliation: Department of Medicine (Solna), Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Science for Life Laboratory, Department of Medical Sciences, Uppsala Unversity, Uppsala, Sweden; nils.landegren@ki.se.
authors.forename: Nils
authors.initials: N
authors.lastname: Landegren
authors.affiliation: Departments of Medical Sciences.
authors.forename: Mina
authors.initials: M
authors.lastname: Pourmousa Lindberg
authors.affiliation: Department of Medicine (Solna), Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Science for Life Laboratory, Department of Medical Sciences, Uppsala Unversity, Uppsala, Sweden.
authors.forename: Jakob
authors.initials: J
authors.lastname: Skov
authors.affiliation: Department of Medicine (Solna), Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Science for Life Laboratory, Department of Medical Sciences, Uppsala Unversity, Uppsala, Sweden.
authors.forename: Åsa
authors.initials: Å
authors.lastname: Hallgren
authors.affiliation: Department of Medicine (Solna), Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Science for Life Laboratory, Department of Medical Sciences, Uppsala Unversity, Uppsala, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Eriksson
authors.affiliation: Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Trine
authors.initials: T
authors.lastname: Lisberg Toft-Bertelsen
authors.affiliation: Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Nanna
authors.initials: N
authors.lastname: MacAulay
authors.affiliation: Departments of Medical Sciences.
authors.forename: Eva
authors.initials: E
authors.lastname: Hagforsen
authors.affiliation: Department of Pathology, Helsinki University Hospital and Helsinki University, Helsinki, Finland.
authors.forename: Anne
authors.initials: A
authors.lastname: Räisänen-Sokolowski
authors.affiliation: Department of Medicine, Tampere University Hospital Medical School, Tampere, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Saha
authors.affiliation: Departments of Medical Sciences.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nilsson
authors.affiliation: Departments of Medical Sciences.
authors.forename: Gunnel
authors.initials: G
authors.lastname: Nordmark
authors.affiliation: Department of Nephrology, Lund University, Lund, Sweden.
authors.forename: Sophie
authors.initials: S
authors.lastname: Ohlsson
authors.affiliation: Women's and Children's Health, and.
authors.forename: Jan
authors.initials: J
authors.lastname: Gustafsson
authors.affiliation: Department of Medicine (Solna), Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Science, University of Bergen and Department of Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Eystein S
authors.initials: ES
authors.lastname: Husebye
authors.affiliation: Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Larsson
authors.affiliation: Diabetes Center, University of California, San Francisco, California.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Anderson
authors.affiliation: The Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland; and.
authors.forename: Jaakko
authors.initials: J
authors.lastname: Perheentupa
authors.affiliation: Departments of Medical Sciences.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Rorsman
authors.affiliation: Interactions of Proteins in Epithelial Transport Center, Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Fenton
authors.affiliation: Department of Medicine (Solna), Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Science for Life Laboratory, Department of Medical Sciences, Uppsala Unversity, Uppsala, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Kämpe
mesh_terms: D000328:Adult; D020346:Aquaporins / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D005260:Female; D006801:Humans; D007685:Kidney Tubules, Collecting / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009395:Nephritis, Interstitial / Q000276:immunology*; D055815:Young Adult
chemical_list: D020346:Aquaporins; D001323:Autoantibodies
keywords: Immunology and pathology; end stage kidney disease; interstitial fibrosis