Linked Life Data

11549658

Source:http://linkedlifedata.com/resource/pubmed/id/11549658

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2001-9-10
pubmed:abstractText
Patients with Graves' disease have autoantibodies that bind to the TSH receptor and stimulate the thyroid, leading to hyperthyroidism. Earlier studies have shown that the ectodomain of the glycosylated human TSH receptor contains epitopes that could adsorb these pathogenic antibodies. Further studies with mutated cDNAs, chimeric proteins, peptides, and antipeptide antibodies suggested that alterations in the conformation of the protein could lead to loss of reactivity, and that thyroid-stimulating antibodies interact with the N-terminal region of the TSH receptor. Although many of these studies provided valuable insights, they were somewhat inconclusive due to limitations inherent to each of the approaches. In an attempt to further define regions within the TSH receptor with which thyroid-stimulating antibodies interact, we expressed seven recombinant TSH receptor fragments in insect cells and tested them for their ability to neutralize TSH binding inhibitory Igs and thyroid-stimulating antibody activity in the sera of patients with Graves' disease. The fragments containing amino acids 22-305 were able to neutralize the TSH binding inhibitory Ig activity, whereas a fragment containing amino acids 54-254 was able to neutralize the thyroid-stimulating antibodies. Fragments containing additional amino acids, flanking residues 54-254, failed to neutralize the thyroid-stimulating antibody activity, suggesting that thyroid-stimulating antibody epitopes are masked. Our studies show that thyroid autoantibodies, with different functional properties, bind to distinct conformational epitopes on the TSH receptor.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-972X
pubmed:author
pubmed:issnType
Print
pubmed:volume
86
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4254-60
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Studies using recombinant fragments of human TSH receptor reveal apparent diversity in the binding specificities of antibodies that block TSH binding to its receptor or stimulate thyroid hormone production.
pubmed:affiliation
Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, Illinois 60612, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't