Autoimmune hypophysitis of SJL mice: clinical insights from a new animal model.
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.
Tzou
Shey-Cherng
SC
Department of Pathology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA.
Lupi
Isabella
I
Landek
Melissa
M
Gutenberg
Angelika
A
Tzou
Ywh-Min
YM
Kimura
Hiroaki
H
Pinna
Giovanni
G
Rose
Noel R
NR
Caturegli
Patrizio
P
D000818:Animals; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D010900:Pituitary Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D010903:Pituitary Gland, Anterior / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D001324:Autoantigens