Pituitary autoantibodies in autoimmune polyendocrine syndrome type 1.
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.
Bensing
Sophie
S
Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden. sophie.bensing@ki.se
Fetissov
Sergueï O
SO
Mulder
Jan
J
Perheentupa
Jaakko
J
Gustafsson
Jan
J
Husebye
Eystein S
ES
Oscarson
Mikael
M
Ekwall
Olov
O
Crock
Patricia A
PA
Hökfelt
Tomas
T
Hulting
Anna-Lena
AL
Kämpe
Olle
O
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
D001323:Autoantibodies; D001324:Autoantigens; D013006:Growth Hormone