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Pituitary autoantibodies in autoimmune polyendocrine syndrome type 1.

Journal article
Authors Sophie Bensing
Sergueï O Fetissov
Jan Mulder
Jaakko Perheentupa
Jan Gustafsson
Eystein S Husebye
Mikael Oscarson
Olov Ekwall
Patricia A Crock
Tomas Hökfelt
Anna-Lena Hulting
Olle Kämpe
Published in Proceedings of the National Academy of Sciences of the United States of America
Volume 104
Issue 3
Pages 949-54
ISSN 0027-8424
Publication year 2007
Published at
Pages 949-54
Language en
Keywords Adolescent, Amino Acid Motifs, Animals, Autoantibodies, immunology, Autoantigens, immunology, Child, Female, Growth Hormone, deficiency, metabolism, Guinea Pigs, Humans, Immunohistochemistry, Immunoprecipitation, Male, Molecular Sequence Data, Pituitary Gland, immunology, pathology, Polyendocrinopathies, Autoimmune, immunology, pathology
Subject categories Clinical immunology, Endocrinology

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.

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