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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8796
pubmed:dateCreated
1992-4-17
pubmed:abstractText
Idiopathic Addison's disease is characterised by a progressive failure in the synthesis of all classes of steroid hormones and by an immune response against the steroid-producing cells of the adrenal cortex; the nature of the adrenal autoantigens is not known. We have used molecular cloning and sequencing to identify the target antigens. We screened a human fetal adrenal cDNA expression library in lambda gt11 vector with serum samples from patients with Addison's disease as part of the type 1 polyendocrine autoimmunity syndrome. Samples from 3 patients, which had precipitating antibodies against two adrenal proteins detected by immunodiffusion and against five adrenal proteins of molecular mass 55, 48, 43, 39, and 19 kDa as judged by immunoblotting, were used to identify 60 immunoreactive clones. 39 of these were subcloned, inserted into the M13mp10 vector, and sequenced by the dideoxy method or identified by Southern and dot-blot hybridisation. All but 1 of the inserts showed more than 98.8% homology with the published sequence of steroid 17 alpha-hydroxylase. This protein was expressed by insertion of 1 of the clones into the pGEMEX-1 vector. Only serum from patients with Addison's disease and type 1 polyendocrine autoimmunity syndrome that reacted with the 55 kDa adrenal protein recognised the recombinant 17 alpha-hydroxylase protein on immunoblotting. Our results show that one of the key enzymes in steroid biosynthesis, 17 alpha-hydroxylase, is an autoantigen involved in the pathogenesis of adrenocortical failure.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0140-6736
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
339
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
770-3
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Identification by molecular cloning of an autoantigen associated with Addison's disease as steroid 17 alpha-hydroxylase.
pubmed:affiliation
Institute of Biomedical Sciences, University of Tampere, Finland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't