The Calcium-sensing Receptor is a Target of Autoantibodies in Patients with Autoimmune Polyendocrine Syndrome Type 1.
From: Section of Endocrinology and Reproduction, School of Medicine and Biomedical Sciences, University of Sheffield, Royal Hallamshire Hospital, Glossop Road, Sheffield, UK.
The Journal of clinical endocrinology and metabolism
- Publish Date: Jun 2007
- ISSN: 0021-972X
- Volume: 92
- Issue: 6
- Pages: 2107-14
- Medium: Print
- Language: English
- Citation (JAMA): Gavalas Nikos G, Kemp E Helen, Krohn Kai J E, et al. The Calcium-sensing Receptor is a Target of Autoantibodies in Patients with Autoimmune Polyendocrine Syndrome Type 1.. J. Clin. Endocrinol. Metab. Jun 2007;92:2107-14
Abstract
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. However, the detection of CaSR antibodies in APS1 remains controversial, with some studies disputing the relevance of the receptor as an autoantigen. OBJECTIVE: The aim of this study was to analyze a defined set of APS1 patient sera for the presence of CaSR antibodies using different assay systems. RESULTS: APS1 patients and individuals with other autoimmune disorders along with healthy subjects were tested for antibody binding to the CaSR. In an immunoprecipitation assay with the CaSR expressed in human embryonic kidney 293 cells, 12 of 14 (85.7%) APS1 and two of 28 (7.1%) Graves’ disease patients were considered positive for CaSR antibodies. The prevalence of receptor antibodies was significantly greater than that in the cohort of healthy individuals only in the APS1 patient group (P < 0.0001). In a flow cytometry assay, seven of 14 (50.0%) APS1 patient sera showed binding to the extracellular domain of the CaSR. The prevalence of receptor antibodies in the APS1 patient group was significantly greater than that in the group of healthy controls (P = 0.023). No CaSR antibodies could be detected in any patients or controls using a radiobinding assay. CONCLUSION: The CaSR is an autoantigen in APS1, but detection of antibodies against the receptor appears to be influenced by the assay system used.
Mesh Headings (Keywords): Adolescent, Adult, Antibody Specificity, Autoantibodies, Cells, Cultured, Child, DNA, Complementary, Female, Flow Cytometry, Glycosylphosphatidylinositols, Humans, Kidney, Male, Middle Aged, Mutagenesis, Plasmids, Polyendocrinopathies, Autoimmune, Protein Structure, Tertiary, Radioimmunoassay, Receptors, Calcium-Sensing, Seroepidemiologic Studies
Check for Full Text / PubMed Unique Identifier (PMID): 17374709
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