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

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.

• Authors: Casey J A Smith-Anttila, Sophie Bensing, Mohammad Alimohammadi, Frida Dalin, Mikael Oscarson, Ming-Dong Zhang, Jaakko Perheentupa, Eystein S Husebye, Jan Gustafsson, Peyman Björklund, Anette Fransson, Gunnel Nordmark, Lars Rönnblom, Antonella Meloni, Rodney J Scott, Tomas Hökfelt, Patricia A Crock, Olle Kämpe
• Journal: Autoimmunity (Autoimmunity) Vol. 50 Issue 4 Pg. 223-231 (Jun 2017) ISSN: 1607-842X [Electronic] England
• PMID: 28557628 (Publication Type: Journal Article)

Chemical References

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

Topics

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