{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T10:39:51Z","timestamp":1779187191397,"version":"3.51.4"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2018,12,1]],"date-time":"2018-12-01T00:00:00Z","timestamp":1543622400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>A major manifestation of autoimmune polyendocrine syndrome type 1 (APS1) is hypoparathyroidism, which is suggested to result from aberrant immune responses against the parathyroid glands. The calcium-sensing receptor (CaSR), which plays a pivotal role in maintaining calcium homeostasis by sensing blood calcium levels and regulating release of parathyroid hormone (PTH), is an autoantibody target in APS1. In this study, the aim was to characterize the binding sites, specificity, functional affinity, IgG subclass, and functional effects of CaSR autoantibodies using phage-display technology, ELISA, and bioassays. The results indicated that CaSR autoantibody binding sites were at aa 41\u201369, 114\u2013126, 171\u2013195, and 260\u2013340 in the extracellular domain of the receptor. Autoantibodies against CaSR epitopes 41\u201369, 171\u2013195, and 260\u2013340 were exclusively of the IgG1 subclass. Autoantibody responses against CaSR epitope 114\u2013126 were predominantly of the IgG1 with a minority of the IgG3 subclass. Only autoantibodies recognizing CaSR epitopes 114\u2013126 and 171\u2013195 affected receptor activity; inositol-phosphate accumulation was increased significantly in HEK293-CaSR cells, and PTH secretion from PTH-C1 cells was reduced significantly when either were incubated with purified Ab and Ca2+ compared with Ca2+ alone. In conclusion, although the majority of APS1 patients do not have CaSR-stimulating autoantibodies, the hypoparathyroid state in a small minority of patients is the result of functional suppression of the parathyroid glands.<\/jats:p>","DOI":"10.4049\/jimmunol.1701527","type":"journal-article","created":{"date-parts":[[2018,10,31]],"date-time":"2018-10-31T15:53:07Z","timestamp":1541001187000},"page":"3175-3183","source":"Crossref","is-referenced-by-count":14,"title":["Calcium-Sensing Receptor Autoantibodies in Patients with Autoimmune Polyendocrine Syndrome Type 1: Epitopes, Specificity, Functional Affinity, IgG Subclass, and Effects on Receptor Activity"],"prefix":"10.1093","volume":"201","author":[{"given":"Mahmoud","family":"Habibullah","sequence":"first","affiliation":[{"name":"Department of Oncology and Metabolism, University of Sheffield , Sheffield S10 2RX ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie A","family":"Porter","sequence":"additional","affiliation":[{"name":"Department of Oncology and Metabolism, University of Sheffield , Sheffield S10 2RX ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5225-8316","authenticated-orcid":false,"given":"Nicolas","family":"Kluger","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Allergology and Venereology, Institute of Clinical Medicine, University of Helsinki and Helsinki University Central Hospital , 00250 Helsinki ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4335-0396","authenticated-orcid":false,"given":"Annamari","family":"Ranki","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Allergology and Venereology, Institute of Clinical Medicine, University of Helsinki and Helsinki University Central Hospital , 00250 Helsinki ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai J E","family":"Krohn","sequence":"additional","affiliation":[{"name":"Clinical Research Institute HUCH Ltd. , 00250 Helsinki ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8741-0592","authenticated-orcid":false,"given":"Maria L","family":"Brandi","sequence":"additional","affiliation":[{"name":"Department of Surgery and Translational Medicine, University of Florence , 50139 Florence ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward M","family":"Brown","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Harvard University , Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony P","family":"Weetman","sequence":"additional","affiliation":[{"name":"Department of Oncology and Metabolism, University of Sheffield , Sheffield S10 2RX ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0313-8916","authenticated-orcid":false,"given":"E Helen","family":"Kemp","sequence":"additional","affiliation":[{"name":"Department of Oncology and Metabolism, University of Sheffield , Sheffield S10 2RX ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,12,1]]},"reference":[{"key":"2025030417575156700_r1","doi-asserted-by":"crossref","first-page":"2843","DOI":"10.1210\/jc.2005-2611","article-title":"Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy","volume":"91","author":"Perheentupa","year":"2006","journal-title":"J. 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