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Autoimmune Hypercalcemia Due to Autoantibodies Against the Calcium-sensing Receptor
- Source :
- JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, instname
- Publication Year :
- 2020
- Publisher :
- ENDOCRINE SOC, 2020.
-
Abstract
- Context Autoimmune hypocalciuric hypercalcemia (AHH) is an acquired disorder caused by the presence of blocking autoantibodies against the calcium-sensing receptor (CaSR). Few cases of this condition have been described to date in the literature. Objective The objectives of this study were to describe 2 patients in whom the presence of AHH was suspected and to assess the patients for the presence of CaSR antibodies. Methods CaSR antibodies were detected and characterised by immunoprecipitation assays, CaSR peptide ELISAs, and functional assays based on the calcium-stimulated accumulation of inositol-1-phosphate in a mammalian cell line expressing the CaSR. Results Both patients presented with an acquired form of hypocalciuric hypercalcemia. Mutational analyses of CASR, GNA11, and AP2S1 for familial hypocalciuric hypercalcemia were negative. According to the presence of Hashimoto’s disease in 1 patient and latent autoimmune diabetes of adulthood and thyroid autoimmunity in the other, AHH was suspected. Immunoprecipitation assays detected CaSR antibodies in both patients. Analysis of the antibody binding sites revealed 2 main epitopes at amino acids 41–69 and 114–126. Preincubation with purified CaSR antibodies against epitope 114–126 resulted in a significant decrease in inositol-1-phophate accumulation upon calcium-stimulation of mammalian cells expressing the CaSR, suggesting that the antibodies had receptor-blocking activity. Conclusions AHH is to be suspected in patients with an acquired biochemical pattern of PTH-dependant hypocalciuric hypercalcemia, especially in those with other concomitant autoimmune diseases. Diagnosis by means of detecting CaSR antibodies may help to better characterise this probably under-reported condition.
- Subjects :
- Male
0301 basic medicine
medicine.medical_specialty
calcium-sensing receptor
Endocrinology, Diabetes and Metabolism
Clinical Biochemistry
030209 endocrinology & metabolism
Context (language use)
Hashimoto Disease
medicine.disease_cause
Biochemistry
Epitope
Autoimmune Diseases
Autoimmunity
hyperparathyroidism
03 medical and health sciences
0302 clinical medicine
Endocrinology
Internal medicine
medicine
Humans
Aged
Autoantibodies
Hyperparathyroidism
Familial hypocalciuric hypercalcemia
biology
business.industry
Biochemistry (medical)
autoimmunity
Autoantibody
Middle Aged
epitopes
medicine.disease
030104 developmental biology
Immunology
Hypercalcemia
biology.protein
Calcium-sensing receptor
Antibody
business
Receptors, Calcium-Sensing
Subjects
Details
- ISSN :
- 0021972X
- Database :
- OpenAIRE
- Journal :
- JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, instname
- Accession number :
- edsair.doi.dedup.....99a469bedf0e89ecfc77ae05b19071a1