title: A missense single-nucleotide polymorphism in the sialic acid acetylesterase (SIAE) gene is associated with anti-PIT-1 antibody syndrome.
abstract: A novel clinical entity related to autoimmune polygladular syndrome (APS) termed "anti-PIT-1 antibody syndrome" is characterized by a presence of circulating autoantibody against the pituitary-specific transcriptional factor-1 (PIT-1) with acquired specific defect in GH, PRL, and TSH. Although autoimmunity to PIT-1 has been suggested, the underlying mechanisms remain to be elucidated. Sialic acid acetylesterase (SIAE) plays a crucial role in regulating the threshold of autoantibody production of B-cells and the defective variants of SIAE are associated with an increased risk of various autoimmune diseases such as type 1 diabetes (T1DM). To explore the link between anti-PIT-1 antibody syndrome and SIAE, we analyzed SIAE gene in 3 patients with anti-PIT-1 antibody syndrome and 200 healthy control subjects, and compared the prevalence of single nucleotide polymorphisms. Intriguingly, we found A467V SIAE variants (c.1400C>T, rs7941523) in a heterozygous state in all the patients with anti-PIT-1 antibody syndrome, while we detected in 6 % of control subjects, in which the prevalence was significantly increased in the patients (P<0.0005). Considering the physiological function of SIAE and the clinical features of anti-PIT-1 antibody syndrome, present data imply a novel aspect of the pathogenesis in this disease.
authors.affiliation: Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Genzo
authors.initials: G
authors.lastname: Iguchi
authors.forename: Hironori
authors.initials: H
authors.lastname: Bando
authors.forename: Hidenori
authors.initials: H
authors.lastname: Fukuoka
authors.forename: Kentaro
authors.initials: K
authors.lastname: Suda
authors.forename: Michiko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nishizawa
authors.forename: Ryusaku
authors.initials: R
authors.lastname: Matsumoto
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Tojo
authors.forename: Atsuko
authors.initials: A
authors.lastname: Mokubo
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Takahashi
mesh_terms: D000115:Acetylesterase / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D001323:Autoantibodies / Q000097:blood* / Q000235:genetics; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010900:Pituitary Diseases / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D013577:Syndrome; D050817:Transcription Factor Pit-1 / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D050817:Transcription Factor Pit-1; D000115:Acetylesterase; C046298:sialate O-acetylesterase