Anti-PTH monoclonal antibody, clone 5D6

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.

Background: Carpal tunnel syndrome (CTS) is one of the most common complications among hemodialysis (HD) patients. This study aimed to assess the prevalence of CTS in HD patients using clinical and noninvasive ultrasound (US) criteria. Methods: A cross-sectional, observational study was conducted on 94 HD patients to evaluate CTS manifestations and demographic, clinical, and laboratory data. The median nerve (MN) cross sectional area (CSA) (MN-CSA) was estimated by US examination at the pisiform and hamate levels. Both hands were evaluated, and the higher MN-CSA was considered. Results: Neuropathic pain and nocturnal numbness at MN distribution were present in 40.4% and 18.1%, respectively, while Tinel's test was positive in 25.5% of patients. A MN-CSA >= 11.5 mm(2) identified the probability of CTS with 63% sensitivity and 80% specificity. Patients with CTS had higher serum calcium (P = 0.02) and lower parathyroid hormone (PTH) (P = 0.02). CTS was frequently developed on the same side of an arteriovenous fistula. The MN-CSA had positive correlations with age, serum phosphorus, and visual analogue scale (VAS) score (P = 0.01, 0.01, and 0.03 respectively) and a negative correlation with PTH level (P = 0.007). Serum phosphorus level (P = 0.015) and VAS (P = 0.04) were the significant predictors of MN-CSA. Conclusion: CTS appears to frequently occur in HD patients. US examination may be helpful in detection of CTS and can be an alternative to electrodiagnostic studies in HD patients.