Calcium-Sensing Receptor Autoantibodies and Idiopathic Hypoparathyroidism

被引:40
|
作者
Tomar, Neeraj [1 ]
Gupta, Nandita [1 ]
Goswami, Ravinder [1 ]
机构
[1] All India Inst Med Sci, Dept Endocrinol & Metab, New Delhi 110029, India
来源
关键词
THYROID AUTOIMMUNITY; PREVALENCE; ANTIBODIES; POLYMORPHISM; TYPE-1; DOMAIN; NALP5; GENE;
D O I
10.1210/jc.2013-2158
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context: Data on calcium-sensing receptor autoantibodies (CaSRAbs) in hypoparathyroidism are variable. Objective: We assessed the prevalence and significance of CaSRAbs in idiopathic hypoparathyroidism. Design: This was a case-control study. Subjects: One hundred forty-seven patients with idiopathic hypoparathyroidism treated during 1998-2011 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. Methods: 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. Results: 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. Conclusion: 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.
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页码:3884 / 3891
页数:8
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