Pituitary autoantibodies in autoimmune polyendocrine syndrome type 1

• Published in: Proceedings of the National Academy of Sciences - PNAS 2007-01, Vol.104 (3), p.949-954
• Main Authors: Bensing, Sophie, Fetissov, Sergueï O, Mulder, Jan, Perheentupa, Jaakko, Gustafsson, Jan, Husebye, Eystein S, Oscarson, Mikael, Ekwall, Olov, Crock, Patricia A, Hökfelt, Tomas, Hulting, Anna-Lena, Kämpe, Olle
• Format: Article
• Language: English
• Subjects: Adolescent; Amino Acid Motifs; Animals; Anterior pituitary; Autoantibodies; Autoantibodies - immunology; Autoantigens; Autoantigens - immunology; Autoimmune diseases; Biological Sciences; Blood donation; Child; Complementary DNA; Disease manifestations; Enzymes; Female; Growth Hormone - deficiency; Growth Hormone - metabolism; Growth hormones; Guinea Pigs; Hormones; Humans; Immune system; Immunohistochemistry; Immunoprecipitation; Libraries; Male; MEDICIN; Medicin och hälsovetenskap; MEDICINE; Molecular Sequence Data; Pituitary gland; Pituitary Gland - immunology; Pituitary Gland - pathology; Pituitary intermediate lobe; Polyendocrinopathies, Autoimmune - immunology; Polyendocrinopathies, Autoimmune - pathology; Proteins; Tudor domain containing protein 6
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.0610070104

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.