Identification of endothelin-converting enzyme-2 as an autoantigen in autoimmune polyendocrine syndrome type 1

Autoimmunity. 2017 Jun;50(4):223-231. doi: 10.1080/08916934.2017.1332183. Epub 2017 May 30.


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.

Keywords: APS1; ECE-2; endothelin-converting enzyme-2; pancreas; pituitary autoantibodies.

MeSH terms

  • Adolescent
  • Alternative Splicing
  • Autoantibodies / immunology
  • Autoantigens / genetics
  • Autoantigens / immunology*
  • Autoimmunity
  • Child
  • Endothelin-Converting Enzymes / genetics
  • Endothelin-Converting Enzymes / immunology*
  • Female
  • Gene Expression
  • Gene Expression Profiling
  • Genetic Loci
  • Humans
  • Immunohistochemistry
  • Male
  • Phenotype
  • Pituitary Gland / immunology
  • Pituitary Gland / metabolism
  • Polyendocrinopathies, Autoimmune / diagnosis
  • Polyendocrinopathies, Autoimmune / genetics
  • Polyendocrinopathies, Autoimmune / immunology*


  • Autoantibodies
  • Autoantigens
  • ECE2 protein, human
  • Endothelin-Converting Enzymes