title: Pituitary autoantibodies in autoimmune polyendocrine syndrome type 1.
abstract: Autoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal recessive disorder caused by mutations in the autoimmune regulator (AIRE) gene. High titer autoantibodies (Aabs) toward intracellular enzymes are a hallmark for APS1 and serve as diagnostic markers and predictors for disease manifestations. In this study, we aimed to identify pituitary autoantigens in patients with APS1. A pituitary cDNA expression library was screened with APS1 sera and a tudor domain containing protein 6 (TDRD6) cDNA clone was isolated. Positive immunoreactivity against in vitro translated TDRD6 fragments was shown in 42/86 (49%) APS1 patients but not in patients with other autoimmune diseases or in healthy controls. By using immunohistochemistry, sera from 3/6 APS1 patients with growth hormone (GH) deficiency showed immunostaining of a small number of guinea pig anterior pituitary cells, and 40-50% of these cells were GH-positive. No such immunostaining was seen with sera from healthy controls. The APS1 Aab-positive, GH-negative cells may represent a novel subpopulation of anterior pituitary cells. In addition, 4/6 patient sera showed staining of a fiber-plexus in the pituitary intermediate lobe recognizing enzymes of monoamine and GABA synthesis. Thus, we have identified TDRD6 as a major autoantigen in APS1 patients and shown that several sera from GH-deficient patients stain specific cell populations and nerves in the pituitary gland.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden. sophie.bensing@ki.se
authors.forename: Sophie
authors.initials: S
authors.lastname: Bensing
authors.forename: Sergueï O
authors.initials: SO
authors.lastname: Fetissov
authors.forename: Jan
authors.initials: J
authors.lastname: Mulder
authors.forename: Jaakko
authors.initials: J
authors.lastname: Perheentupa
authors.forename: Jan
authors.initials: J
authors.lastname: Gustafsson
authors.forename: Eystein S
authors.initials: ES
authors.lastname: Husebye
authors.forename: Mikael
authors.initials: M
authors.lastname: Oscarson
authors.forename: Olov
authors.initials: O
authors.lastname: Ekwall
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Crock
authors.forename: Tomas
authors.initials: T
authors.lastname: Hökfelt
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Hulting
authors.forename: Olle
authors.initials: O
authors.lastname: Kämpe
mesh_terms: D000293:Adolescent; D020816:Amino Acid Motifs; D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D002648:Child; D005260:Female; D013006:Growth Hormone / Q000172:deficiency / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008297:Male; D008969:Molecular Sequence Data; D010902:Pituitary Gland / Q000276:immunology* / Q000473:pathology; D016884:Polyendocrinopathies, Autoimmune / Q000276:immunology* / Q000473:pathology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D013006:Growth Hormone