Autoimmune Hypercalcemia Due to Autoantibodies Against the Calcium-sensing Receptor

Area of Science:

• Endocrinology
• Immunology
• Molecular Biology

Background:

• Autoimmune hypocalciuric hypercalcemia (AHH) is a rare acquired disorder resulting from autoantibodies targeting the calcium-sensing receptor (CaSR).
• Few cases of AHH have been documented, highlighting the need for better understanding and diagnostic approaches.

Observation:

• Two patients presented with acquired hypocalciuric hypercalcemia, with negative genetic testing for familial forms.
• Both patients had co-existing autoimmune conditions (Hashimoto's disease and latent autoimmune diabetes/thyroid autoimmunity).
• CaSR antibodies were detected in both patients using immunoprecipitation and ELISA assays.

Findings:

• CaSR antibodies targeted specific epitopes (amino acids 41-69 and 114-126).
• Antibodies against epitope 114-126 demonstrated receptor-blocking activity in functional assays, inhibiting calcium-stimulated signaling.
• These findings confirm the pathogenic role of CaSR autoantibodies in AHH.

Implications:

• AHH should be suspected in patients with acquired hypocalciuric hypercalcemia, particularly those with other autoimmune diseases.
• Detecting CaSR antibodies is crucial for diagnosing and characterizing AHH, potentially identifying an under-reported condition.
• This research contributes to understanding CaSR-related disorders and autoimmune mechanisms in hypercalcemia.