SFEBES2009 Poster Presentations Thyroid (59 abstracts)
Epitopes for calcium-sensing receptor antibodies in patients with autoimmune polyendocrine syndrome type 1 are located in the N-terminal of the extracellular domain
EH Kemp 1 , NG Gavalas 1 , S Akhtar 1 , KJE Krohn 2 , EM Brown 3 , P Watson 1 & AP Weetman 1
1University of Sheffield, Sheffield, UK; 2University of Tampere, Tampere, Finland; 3Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Context: Autoimmune polyendocrine syndrome type 1 (APS1) is an autosomal recessive disorder caused by mutations in the autoimmune regulator gene. Hypoparathyroidism occurs in 80% of patients with APS1 and has been suggested to result from an autoimmune reaction against the calcium-sensing receptor (CaSR) on parathyroid cells. Previously, we have detected CaSR-binding antibodies in patients with APS1 using immunoprecipitation and flow cytometry assays.
Objective: The aim of this study was to define the binding domains of APS1 patient CaSR antibodies.
Methods: A phage-display CaSR peptide library was used to screen APS1 patient sera (n=14) in biopanning experiments in order to identify receptor peptides recognised by CaSR antibodies. Antibody reactivity to identified peptides was tested in ELISA, with sera from healthy individuals (n=20) being used as control samples.
Results: Antibody reactivity to CaSR peptides 41–69, 114–126 and 171–195 was identified by phage-display technology and subsequently confirmed in ELISA in 12/14 (86%), 5/14 (36%) and 4/14 (29%) of APS1 patients, respectively. Antibody reactivity was not detected in control sera. The prevalence of receptor antibodies to the each of the specific CaSR peptides was found to be significantly greater in the APS1 patient group than in the cohort of healthy individuals (P<0.0001, P=0.0072 and 0.0216, respectively).
Conclusion: The present work has demonstrated the successful use of phage-display technology in the discovery of CaSR-specific epitopes targeted by antibodies in APS1 patients. The results suggest that a major epitope for APS1 patient CaSR antibodies is localised in the N-terminal (amino acid residues 41–69) of the extracellular domain of the receptor.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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