Autoimmune hypophysitis of SJL mice: Clinical insights from a new animal model

Shey Cherng Tzou, Isabella Lupi, Melissa Landek, Angelika Gutenberg, Ywh Min Tzou, Hiroaki Kimura, Giovanni Pinna, Noel R. Rose, Patrizio P Caturegli

Research output: Contribution to journalArticle

Abstract

Autoimmune hypophysitis (AH) is a rare but increasingly recognized disease of the pituitary gland. Its autoantigens are unknown, and the management is difficult because it is often misdiagnosed as a nonsecreting adenoma. By immunizing female SJL/J mice with mouse pituitary extracts, we established a new mouse model of experimental AH. Immunized mice developed severe lymphocytic infiltration in the anterior pituitary that closely mimicked the human pathology. In the early phase of experimental AH, the pituitary enlarged, consistent with the compression symptoms reported by hypophysitis patients at presentation. In the florid phase, adrenal insufficiency and pituitary antibodies developed, in strong correlation with the pituitary pathology. In the late phase, hypothyroidism ensued, and the pituitary gland became atrophic. Using immune sera as probes in a two-dimensional immunoblotting screen followed by mass spectrometry, we identified several proteins that could function as pituitary autoantigens. These findings provide new insights into the pathogenesis of AH, and establish a platform for developing novel diagnostic biomarkers and therapeutics.

Original languageEnglish (US)
Pages (from-to)3461-3469
Number of pages9
JournalEndocrinology
Volume149
Issue number7
DOIs
StatePublished - Jul 2008

Fingerprint

Animal Models
Autoantigens
Pituitary Diseases
Pathology
Adrenal Insufficiency
Pituitary Gland
Hypothyroidism
Diagnostic Errors
Immunoblotting
Adenoma
Immune Sera
Mass Spectrometry
Theoretical Models
Biomarkers
Autoimmune Hypophysitis
Antibodies
Proteins
Therapeutics

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Tzou, S. C., Lupi, I., Landek, M., Gutenberg, A., Tzou, Y. M., Kimura, H., ... Caturegli, P. P. (2008). Autoimmune hypophysitis of SJL mice: Clinical insights from a new animal model. Endocrinology, 149(7), 3461-3469. https://doi.org/10.1210/en.2007-1692

Autoimmune hypophysitis of SJL mice : Clinical insights from a new animal model. / Tzou, Shey Cherng; Lupi, Isabella; Landek, Melissa; Gutenberg, Angelika; Tzou, Ywh Min; Kimura, Hiroaki; Pinna, Giovanni; Rose, Noel R.; Caturegli, Patrizio P.

In: Endocrinology, Vol. 149, No. 7, 07.2008, p. 3461-3469.

Research output: Contribution to journalArticle

Tzou, SC, Lupi, I, Landek, M, Gutenberg, A, Tzou, YM, Kimura, H, Pinna, G, Rose, NR & Caturegli, PP 2008, 'Autoimmune hypophysitis of SJL mice: Clinical insights from a new animal model', Endocrinology, vol. 149, no. 7, pp. 3461-3469. https://doi.org/10.1210/en.2007-1692
Tzou SC, Lupi I, Landek M, Gutenberg A, Tzou YM, Kimura H et al. Autoimmune hypophysitis of SJL mice: Clinical insights from a new animal model. Endocrinology. 2008 Jul;149(7):3461-3469. https://doi.org/10.1210/en.2007-1692
Tzou, Shey Cherng ; Lupi, Isabella ; Landek, Melissa ; Gutenberg, Angelika ; Tzou, Ywh Min ; Kimura, Hiroaki ; Pinna, Giovanni ; Rose, Noel R. ; Caturegli, Patrizio P. / Autoimmune hypophysitis of SJL mice : Clinical insights from a new animal model. In: Endocrinology. 2008 ; Vol. 149, No. 7. pp. 3461-3469.
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