title: Anti-pituitary antibodies against corticotrophs in IgG4-related hypophysitis.
abstract: OBJECTIVE
  IgG4-related disease is a systemic inflammatory disease characterized by infiltration of IgG4-positive plasma cells into multiple organs, including the pituitary gland. Autoimmunity is thought to be involved in the pathogenesis of IgG4-related disease. The diagnosis of IgG4-related hypophysitis (IgG4-RH) is difficult because its clinical features, such as pituitary swelling and hypopituitarism, are similar to those of other pituitary diseases, including lymphocytic hypophysitis and sellar/suprasellar tumors. The presence and significance of anti-pituitary antibodies (APA) in IgG4-RH is unclear.
  
  
  METHODS
  In this case-control study, we used single indirect immunofluorescence on human pituitary substrates to assess the prevalence of serum APA in 17 patients with IgG4-RH, 8 control patients with other pituitary diseases (lymphocytic infundibulo-neurohypophysitis, 3; craniopharyngioma, 2; germinoma, 3), and 9 healthy subjects. We further analyzed the endocrine cells targeted by the antibodies using double indirect immunofluorescence.
  
  
  RESULTS
  APA were found in 5 of 17 patients with IgG4-RH (29%), and in none of the pituitary controls or healthy subjects. The endocrine cells targeted by the antibodies in the 5 IgG4-RH cases were exclusively corticotrophs. Antibodies were of the IgG1 subclass, rather than IgG4, in all 5 cases, suggesting that IgG4 is not directly involved in the pathogenesis. Finally, antibodies recognized pro-opiomelanocortin in 2 of the cases.
  
  
  CONCLUSIONS
  Our study suggests that autoimmunity is involved in the pathogenesis of IgG4-RH and that corticotrophs are the main antigenic target, highlighting a possible new diagnostic marker for this condition.
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Iwata
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan. siwama@med.nagoya-u.ac.jp.|Research Center of Health, Physical Fitness and Sports, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan. siwama@med.nagoya-u.ac.jp.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Iwama
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Sugimura
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Yasuda
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Nakashima
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Takeuchi
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hagiwara
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Suga
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
authors.forename: Motomitsu
authors.initials: M
authors.lastname: Goto
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Banno
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, MD, 21205, USA.|Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.
authors.forename: Patrizio
authors.initials: P
authors.lastname: Caturegli
authors.affiliation: Research Center of Health, Physical Fitness and Sports, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan.
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Koike
authors.affiliation: Research Center of Health, Physical Fitness and Sports, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Oshida
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arima
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000627:therapeutic use*; D000069281:Autoimmune Hypophysitis / Q000188:drug therapy* / Q000276:immunology*; D016022:Case-Control Studies; D052680:Corticotrophs / Q000276:immunology*; D003346:Corticotropin-Releasing Hormone / Q000097:blood; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D013007:Growth Hormone-Releasing Hormone / Q000097:blood; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010900:Pituitary Diseases / Q000188:drug therapy / Q000276:immunology*; D010902:Pituitary Gland / Q000187:drug effects / Q000276:immunology; D013973:Thyrotropin-Releasing Hormone / Q000097:blood; D055815:Young Adult
chemical_list: D000906:Antibodies; D007074:Immunoglobulin G; D013973:Thyrotropin-Releasing Hormone; D003346:Corticotropin-Releasing Hormone; D013007:Growth Hormone-Releasing Hormone