{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T21:08:25Z","timestamp":1774645705293,"version":"3.50.1"},"reference-count":33,"publisher":"The Endocrine Society","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,9,1]]},"abstract":"<jats:sec><jats:title>Context:<\/jats:title><jats:p>Data on calcium-sensing receptor autoantibodies (CaSRAbs) in hypoparathyroidism are variable.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective:<\/jats:title><jats:p>We assessed the prevalence and significance of CaSRAbs in idiopathic hypoparathyroidism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design:<\/jats:title><jats:p>This was a case-control study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Subjects:<\/jats:title><jats:p>One hundred forty-seven patients with idiopathic hypoparathyroidism treated during 1998\u20132011 in a tertiary care setting and 348 controls [healthy, n = 199; type 1 diabetes mellitus (T1DM), n = 99; and chronic lymphocytic thyroiditis (CLT), n = 50] participated in the study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p>CaSRAb assays included Western blot with CaSR protein expressed in Escherichia coli or human embryonic kidney (HEK)-293 cells, immunoprecipitation (IP) using in vitro-transcribed\/translated protein, and indirect immunofluorescence on HEK293-CaSR. Functional significance was assessed by ERK1\/2 phosphorylation. PTH and CaSR genes were sequenced for mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>E coli-Western blot assay revealed 16.3% CaSRAb positivity in idiopathic hypoparathyroidism, which was comparable with healthy subjects and CLT but significantly less than the T1DM controls. The prevalence of CaSRAbs on HEK293-Western blot (24.5%) against 150 kDa and\/or 168 kDa protein in hypoparathyroidism was significantly higher than the healthy subjects, T1DM, and CLT. IP assay showed CaSRAbs in 12.9% of the hypoparathyroid patients but not in controls. The sensitivity and specificity of CaSRAbs in E coli and HEK-293-CaSR Western blot and IP assays were 16.3% and 83.1%, 24.5% and 88.9%, and 12.9% and 100%, respectively, and 42.1% of the cases detected were common in the IP assay and HEK293-Western blot. Duration of illness and coexistent autoimmunity were similar in patients with and without CaSRAbs. The CaSRAb-positive sera showed no immunofluorescence and phosphorylated ERK1\/2 activity. The CaSR gene sequence was normal in all patients. One of the patients showed a novel p.Met1_Asp6del mutation in the signal peptide region of the PTH gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion:<\/jats:title><jats:p>IP performed the best in detecting CaSRAbs in 12.9% of hypoparathyroid patients. Although CaSRAbs were functionally inert, its clinical relevance remains due to 100% specificity. Limited prevalence of CaSRAb suggests heterogeneity in the etiology of idiopathic hypoparathyroidism or the presence of CaSR epitopes other than those measured in the current study.<\/jats:p><\/jats:sec>","DOI":"10.1210\/jc.2013-2158","type":"journal-article","created":{"date-parts":[[2013,7,20]],"date-time":"2013-07-20T05:49:58Z","timestamp":1374299398000},"page":"3884-3891","source":"Crossref","is-referenced-by-count":52,"title":["Calcium-Sensing Receptor Autoantibodies and Idiopathic Hypoparathyroidism"],"prefix":"10.1210","volume":"98","author":[{"given":"Neeraj","family":"Tomar","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism All India Institute of Medical Sciences, New Delhi 110029, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nandita","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism All India Institute of Medical Sciences, New Delhi 110029, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ravinder","family":"Goswami","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism All India Institute of Medical Sciences, New Delhi 110029, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071615140073400_B1","first-page":"119","article-title":"The incidence of parathyroid and other antibodies in the sera of patients with idiopathic hypoparathyroidism","volume":"1","author":"Blizzard","year":"1966","journal-title":"Clin Exp Immunol"},{"key":"2020071615140073400_B2","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1172\/JCI118511","article-title":"Is idiopathic hyperparathyroidism an autoimmune disease?","volume":"97","author":"Rose","year":"1996","journal-title":"J Clin Invest"},{"key":"2020071615140073400_B3","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/B978-012098651-4\/50049-3","article-title":"The hypoparathyroid states","volume-title":"The Parathyroid: Basics and Clinical Aspect","author":"Downs","year":"2001","edition":"2nd ed"},{"key":"2020071615140073400_B4","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1056\/NEJMcp0803050","article-title":"Clinical practice. Hypoparathyroidism","volume":"359","author":"Shoback","year":"2008","journal-title":"N Engl J Med"},{"key":"2020071615140073400_B5","doi-asserted-by":"crossref","first-page":"4840","DOI":"10.1210\/jc.2004-0273","article-title":"Parathyroid hormone gene polymorphism and sporadic idiopathic hypoparathyroidism","volume":"89","author":"Goswami","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615140073400_B6","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1111\/j.1365-2265.2006.02604.x","article-title":"Absence of pathogenic calcium sensing receptor gene mutations in sporadic idiopathic hypoparathyroidism","volume":"65","author":"Sarin","year":"2006","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071615140073400_B7","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1530\/EJE-09-0303","article-title":"Presence and significance of a R110W mutation in the DNA-binding domain of GCM2 gene in patients with isolated hypoparathyroidism and their family members","volume":"162","author":"Tomar","year":"2010","journal-title":"Eur J Endocrinol"},{"key":"2020071615140073400_B8","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1172\/JCI118513","article-title":"Autoantibodies to the extracellular domain of the calcium sensing receptor in patients with acquired hypoparathyroidism","volume":"97","author":"Li","year":"1996","journal-title":"J Clin Invest"},{"key":"2020071615140073400_B9","doi-asserted-by":"crossref","first-page":"4484","DOI":"10.1210\/jc.2004-0021","article-title":"Calcium-sensing receptor autoantibodies are relevant markers of acquired hypoparathyroidism","volume":"89","author":"Mayer","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615140073400_B10","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1530\/eje.0.1500009","article-title":"Prevalence of calcium sensing receptor autoantibodies in patients with sporadic idiopathic hypoparathyroidism","volume":"150","author":"Goswami","year":"2004","journal-title":"Eur J Endocrinol"},{"key":"2020071615140073400_B11","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1210\/jc.2006-2466","article-title":"The calcium-sensing receptor is a target of autoantibodies in patients with autoimmune polyendocrine syndrome type 1","volume":"92","author":"Gavalas","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615140073400_B12","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1210\/jc.2003-030279","article-title":"Prevalence and clinical associations of 10 defined autoantibodies in autoimmune polyendocrine syndrome type I","volume":"89","author":"Soderbergh","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615140073400_B13","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1056\/NEJMoa0706487","article-title":"Autoimmune polyendocrine syndrome type 1 and NALP5, a parathyroid autoantigen","volume":"358","author":"Alimohammadi","year":"2008","journal-title":"N Engl J Med"},{"key":"2020071615140073400_B14","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1210\/jc.2011-3093","article-title":"Prevalence and significance of NALP5 autoantibodies in patients with idiopathichypoparathyroidism","volume":"97","author":"Tomar","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615140073400_B15","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1017\/S0007114509220824","article-title":"Prevalence of vitamin D deficiency and its relationship with thyroid autoimmunity in Asian Indians: a community-based survey","volume":"102","author":"Goswami","year":"2009","journal-title":"Br J Nutr"},{"key":"2020071615140073400_B16","doi-asserted-by":"crossref","first-page":"4256","DOI":"10.1210\/jc.2006-1005","article-title":"Prevalence of thyroid autoimmunity in sporadic idiopathic hypoparathyroidism in comparison to type 1 diabetes and premature ovarian failure","volume":"91","author":"Goswami","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615140073400_B17","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1056\/NEJM199210083271506","article-title":"Brief report: autosomal dominant familial hypoparathyroidism, sensorineural deafness, and renal dysplasia","volume":"327","author":"Bilous","year":"1992","journal-title":"N Engl J Med"},{"key":"2020071615140073400_B18","first-page":"1.116","article-title":"Plasmids and their usefulness in molecular cloning","volume-title":"Molecular Cloning\u2014A Laboratory Manual","author":"Sambrook","year":"2001","edition":"3rd ed"},{"key":"2020071615140073400_B19","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1038\/sj.ki.5002156","article-title":"R990G polymorphism of calcium-sensing receptor does produce a gain-of-function and predispose to primary hypercalciuria","volume":"71","author":"Vezzoli","year":"2007","journal-title":"Kidney Int"},{"key":"2020071615140073400_B20","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1210\/jc.2003-031054","article-title":"Activating antibodies to the calcium-sensing receptor in two patients with autoimmune hypoparathyroidism","volume":"89","author":"Kifor","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615140073400_B21","volume-title":"Antibodies: a laboratory manual","author":"Harlow","year":"1988"},{"key":"2020071615140073400_B22","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1172\/JCI119359","article-title":"Markedly reduced activity of mutant calcium-sensing receptor with an inserted Alu element from a kindred with familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism","volume":"99","author":"Bai","year":"1997","journal-title":"J Clin Invest"},{"key":"2020071615140073400_B23","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1152\/ajpendo.00143.2002","article-title":"PTHrP stimulated by the calcium-sensing receptor requires MAP kinase activation","volume":"284","author":"MacLeod","year":"2003","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2020071615140073400_B24","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1359\/jbmr.090703","article-title":"Mapping of human autoantibody binding sites on the calcium-sensing receptor","volume":"25","author":"Kemp","year":"2010","journal-title":"J Bone Miner Res"},{"key":"2020071615140073400_B25","first-page":"353","article-title":"Demonstration and characterization of anti-human mitochondria autoantibodies in idiopathic hypoparathyroidism and in other conditions","volume":"62","author":"Betterle","year":"1985","journal-title":"Clin Exp Immunol"},{"key":"2020071615140073400_B26","doi-asserted-by":"crossref","first-page":"4749","DOI":"10.1210\/jc.2009-1080","article-title":"Activating autoantibodies against the calcium-sensing receptor detected in two patients with autoimmune polyendocrine syndrome type 1","volume":"94","author":"Kemp","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615140073400_B27","doi-asserted-by":"crossref","first-page":"4602","DOI":"10.1210\/jc.2003-030700","article-title":"The hypoparathyroidism of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy protective effect of male sex","volume":"88","author":"Gylling","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615140073400_B28","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1006\/clin.1994.1051","article-title":"Autoantigenic properties of native and denatured glutamic acid decarboxylase: evidence for a conformational epitope","volume":"71","author":"Tuomi","year":"1994","journal-title":"Clin Immunol Immunopathol"},{"key":"2020071615140073400_B29","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/BF00580656","article-title":"Occurrence and significance of precipitating antibodies against thermophilic actinomycetes in the sera of dairy herd workers, Nangali, Delhi","volume":"59","author":"Gangwar","year":"1991","journal-title":"Antonie Van Leeuwenhoek"},{"key":"2020071615140073400_B30","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1099\/00222615-9-1-63","article-title":"Clostridia isolated from faeces","volume":"9","author":"Drasar","year":"1976","journal-title":"J Med Microbiol"},{"key":"2020071615140073400_B31","doi-asserted-by":"crossref","first-page":"8366","DOI":"10.1073\/pnas.83.21.8366","article-title":"Antibodies cytotoxic to bovine parathyroid cells in autoimmune hypoparathyroidism","volume":"83","author":"Brandi","year":"1986","journal-title":"PNAS"},{"key":"2020071615140073400_B32","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1210\/jc.2007-2042","article-title":"Antithyroperoxidase antibody-dependent cytotoxicity in autoimmune thyroid disease","volume":"93","author":"Rebuffat","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615140073400_B33","doi-asserted-by":"crossref","first-page":"E1820","DOI":"10.1210\/jc.2012-1328","article-title":"Presence of strong association of the major histocompatibility complex (MHC) class I allele HLA-A*26:01 with idiopathic hypoparathyroidism","volume":"97","author":"Goswami","year":"2012","journal-title":"J Clin Endocrinol Metab"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/98\/9\/3884\/11127705\/jcem3884.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/98\/9\/3884\/11127705\/jcem3884.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T10:15:33Z","timestamp":1688379333000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/98\/9\/3884\/2833669"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,9,1]]},"references-count":33,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2013,9,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2013-2158","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,9,1]]}}}