Anti-pituitary antibodies against corticotrophs in IgG4-related hypophysitis

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Purpose: 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.

Original languageEnglish
Pages (from-to)301-310
Number of pages10
JournalPituitary
Volume20
Issue number3
DOIs
Publication statusPublished - 01-06-2017

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Corticotrophs
Anti-Idiotypic Antibodies
Immunoglobulin G
Pituitary Diseases
Endocrine Cells
Antibodies
Indirect Fluorescent Antibody Technique
Autoimmunity
Healthy Volunteers
Germinoma
Craniopharyngioma
Pro-Opiomelanocortin
Hypopituitarism
Pituitary Gland
Plasma Cells
Autoimmune Hypophysitis
Case-Control Studies
Serum

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Iwata, N., Iwama, S., Sugimura, Y., Yasuda, Y., Nakashima, K., Takeuchi, S., ... Arima, H. (2017). Anti-pituitary antibodies against corticotrophs in IgG4-related hypophysitis. Pituitary, 20(3), 301-310. https://doi.org/10.1007/s11102-016-0780-8
Iwata, Naoko ; Iwama, Shintaro ; Sugimura, Yoshihisa ; Yasuda, Yoshinori ; Nakashima, Kohtaro ; Takeuchi, Seiji ; Hagiwara, Daisuke ; Ito, Yoshihiro ; Suga, Hidetaka ; Goto, Motomitsu ; Banno, Ryoichi ; Caturegli, Patrizio ; Koike, Teruhiko ; Oshida, Yoshiharu ; Arima, Hiroshi. / Anti-pituitary antibodies against corticotrophs in IgG4-related hypophysitis. In: Pituitary. 2017 ; Vol. 20, No. 3. pp. 301-310.
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abstract = "Purpose: 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.",
author = "Naoko Iwata and Shintaro Iwama and Yoshihisa Sugimura and Yoshinori Yasuda and Kohtaro Nakashima and Seiji Takeuchi and Daisuke Hagiwara and Yoshihiro Ito and Hidetaka Suga and Motomitsu Goto and Ryoichi Banno and Patrizio Caturegli and Teruhiko Koike and Yoshiharu Oshida and Hiroshi Arima",
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Iwata, N, Iwama, S, Sugimura, Y, Yasuda, Y, Nakashima, K, Takeuchi, S, Hagiwara, D, Ito, Y, Suga, H, Goto, M, Banno, R, Caturegli, P, Koike, T, Oshida, Y & Arima, H 2017, 'Anti-pituitary antibodies against corticotrophs in IgG4-related hypophysitis', Pituitary, vol. 20, no. 3, pp. 301-310. https://doi.org/10.1007/s11102-016-0780-8

Anti-pituitary antibodies against corticotrophs in IgG4-related hypophysitis. / Iwata, Naoko; Iwama, Shintaro; Sugimura, Yoshihisa; Yasuda, Yoshinori; Nakashima, Kohtaro; Takeuchi, Seiji; Hagiwara, Daisuke; Ito, Yoshihiro; Suga, Hidetaka; Goto, Motomitsu; Banno, Ryoichi; Caturegli, Patrizio; Koike, Teruhiko; Oshida, Yoshiharu; Arima, Hiroshi.

In: Pituitary, Vol. 20, No. 3, 01.06.2017, p. 301-310.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Anti-pituitary antibodies against corticotrophs in IgG4-related hypophysitis

AU - Iwata, Naoko

AU - Iwama, Shintaro

AU - Sugimura, Yoshihisa

AU - Yasuda, Yoshinori

AU - Nakashima, Kohtaro

AU - Takeuchi, Seiji

AU - Hagiwara, Daisuke

AU - Ito, Yoshihiro

AU - Suga, Hidetaka

AU - Goto, Motomitsu

AU - Banno, Ryoichi

AU - Caturegli, Patrizio

AU - Koike, Teruhiko

AU - Oshida, Yoshiharu

AU - Arima, Hiroshi

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Purpose: 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.

AB - Purpose: 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.

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U2 - 10.1007/s11102-016-0780-8

DO - 10.1007/s11102-016-0780-8

M3 - Article

C2 - 27896569

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VL - 20

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JO - Pituitary

JF - Pituitary

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