Calcium-Sensing Receptor Autoantibodies and Idiopathic Hypoparathyroidism

Author:

Tomar Neeraj1,Gupta Nandita1,Goswami Ravinder1

Affiliation:

1. Department of Endocrinology and Metabolism All India Institute of Medical Sciences, New Delhi 110029, India

Abstract

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.

Publisher

The Endocrine Society

Subject

Biochemistry, medical,Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

Reference33 articles.

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