Anti-pituitary antibodies against corticotrophs in IgG4-related hypophysitis

• DOI: 10.1007/s11102-016-0780-8
• Publication Date: 2016-11-28T06:51:47Z
• Authors: Naoko Iwata; Shintaro Iwama; Yoshihisa Sugimura; Yoshinori Yasuda; Kohtaro Nakashima; Seiji Takeuchi; Daisuke Hagiwara; Yoshihiro Ito; Hidetaka Suga; Motomitsu Goto; Ryoichi Banno; Patrizio Caturegli; Teruhiko Koike; Yoshiharu Oshida; Hiroshi Arima
• Keywords: Adult; Aged, 80 and over; Male; Adolescent; Corticotropin-Releasing Hormone; Pituitary Diseases; Middle Aged; Growth Hormone-Releasing Hormone; Antibodies; 3. Good health; Young Adult; 03 medical and health sciences; 0302 clinical medicine; Case-Control Studies; Immunoglobulin G; Pituitary Gland; Humans; Autoimmune Hypophysitis; Female; Fluorescent Antibody Technique, Indirect; Corticotrophs; Thyrotropin-Releasing Hormone; Aged

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.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.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.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.