Identification of endothelin-converting enzyme-2 as an autoantigen in autoimmune polyendocrine syndrome type 1.
Autoimmunity
; 50(4): 223-231, 2017 Jun.
Article
in En
| MEDLINE
| ID: mdl-28557628
ABSTRACT
Autoimmune polyendocrine syndrome type 1 (APS1) is a rare monogenic autoimmune disorder caused by mutations in the autoimmune regulator (AIRE) gene. High titer autoantibodies are a characteristic feature of APS1 and are often associated with particular disease manifestations. Pituitary deficits are reported in up to 7% of all APS1 patients, with immunoreactivity to pituitary tissue frequently reported. We aimed to isolate and identify specific pituitary autoantigens in patients with APS1. Immunoscreening of a pituitary cDNA expression library identified endothelin-converting enzyme (ECE)-2 as a potential candidate autoantigen. Immunoreactivity against ECE-2 was detected in 46% APS1 patient sera, with no immunoreactivity detectable in patients with other autoimmune disorders or healthy controls. Quantitative-PCR showed ECE-2 mRNA to be most abundantly expressed in the pancreas with high levels also in the pituitary and brain. In the pancreas ECE-2 was co-expressed with insulin or somatostatin, but not glucagon and was widely expressed in GH producing cells in the guinea pig pituitary. The correlation between immunoreactivity against ECE-2 and the major recognized clinical phenotypes of APS1 including hypopituitarism was not apparent. Our results identify ECE-2 as a specific autoantigen in APS1 with a restricted neuroendocrine distribution.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Autoantigens
/
Polyendocrinopathies, Autoimmune
/
Endothelin-Converting Enzymes
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Adolescent
/
Child
/
Female
/
Humans
/
Male
Language:
En
Year:
2017
Type:
Article