Case report: a 10-year-old girl with primary hypoparathyroidism and systemic lupus erythematosus.

Objectives Hypoparathyroidism is a rare disease in children that occurs as a result of autoimmune destruction of the parathyroid glands, a defect in parathyroid gland development or secondary to physical parathyroid gland disturbance. Typical symptoms of hypoparathyroidism present as hypocalcaemia and hyperphosphatemia due to decreased parathyroid hormone secretion and may lead to nerve and muscles disturbances resulting in clinical manifestation of tetany, arrhythmias and epilepsy. Currently, there is no conventional hormone replacement treatment for hypoparathyroidism and therapeutic approaches include normalising mineral levels using an oral calcium supplement and active forms of vitamin D. Case presentation We present the case of a 10-year-old girl with primary hypoparathyroidism who had no prior history of autoimmune disorders, but who subsequently developed systemic lupus erythematosus.

Severe Symptomatic Hypocalcemia from HIV Related Hypoparathyroidism.

We report the case of a 54-year-old Caucasian female who presented with a two-year history of persistent hypocalcemia requiring multiple hospitalizations. Her medical history was significant for HIV diagnosed four years ago. She denied any history of prior neck surgery or radiation. Her vital signs were stable with an unremarkable physical exam. Pertinent medications included calcium carbonate, vitamin D3, calcitriol, efavirenz, emtricitabine, tenofovir disoproxil, hydrochlorothiazide, and inhaled budesonide/formoterol. Laboratory testing showed total calcium of 5.7 mg/dL (normal range: 8.4-10.2 mg/dL), ionized calcium of 2.7 mg/dL (normal range: 4.5-5.5 mg/dL), serum phosphate of 6.3 mg/dL (normal range: 2.7-4.5 mg/dL), and intact PTH of 7.6 pg/mL (normal range: 15-65 pg/mL). She was diagnosed with primary hypoparathyroidism. Anti-calcium-sensing receptor antibodies and NALP5 antibodies were tested and found to be negative. During subsequent clinic visits, doses of calcium supplements and calcitriol were titrated. Last corrected serum calcium level was 9.18 mg/dL. She was subsequently lost to follow-up. This case gives insight into severe symptomatic hypocalcemia from primary hypoparathyroidism attributed to HIV infection. We suggest that calcium levels should be closely monitored in patients with HIV infection.

Real-time detection of stress in 3D tissue-engineered constructs using NF-kappaB activation in transiently transfected human dermal fibroblast cells.

The main objective of this study was to develop a nondestructive reporter system for assessing the response of human cells contained within a three-dimensional (3D) tissue-engineered construct to exogenous stress. Dermal fibroblasts were transiently transfected with a reporter construct linked to nuclear factor kappaB (NF-kappaB) activation which led to expression of a nonstable form of enhanced green fluorescent protein (d2EGFP) after stimulation. This led to a temporary production of fluorescence, which could be readily detected but was not intrinsically toxic, as cells were able to metabolize the initial cycle of d2EGFP produced. This permitted the model to be used for restimulation post recovery. To investigate the performance and predictive ability of this method for assessing cellular response to stress in 3D, we used a range of compounds known to have pro-inflammatory or oxidative properties. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1beta) were selected for having a direct cytokine action; lipopolysaccharide (LPS) was selected for modeling bacterial-mediated inflammation; and hydrogen peroxide was selected as a crude method for delivering an oxidative stress. Transfected cells were stimulated with the above compounds in 3D and the synthesis of d2EGFP was detected as a measure of NF-kappaB activation. The resultant fluorescence was scored using a series of photomicrographs taken by epifluorescence microscopy. All agents activated NF-kappaB when cells were grown in 3D scaffolds but did not cause any significant reduction in cell viability as measured by a standard MTT-ESTA viability test. Parallel NF-kappaB activation and MTT measurements was also conducted in two-dimension (2D) and confirmed findings in 3D. The 3D model described using a fluorescent reporter gene is a highly sensitive and reliable method for detecting cellular stress and represents a key step in developing tissue engineering models with the potential for screening pharmaceutical and cosmetic compounds, as an alternative to existing in vitro and in vivo methods.

The calcium-sensing receptor is a target of autoantibodies in patients with autoimmune polyendocrine syndrome type 1.

CONTEXT: Autoimmune polyendocrine syndrome type 1 (APS1) is an autosomal recessive disorder caused by mutations in the autoimmune regulator gene. Hypoparathyroidism occurs in 80% of patients with APS1 and has been suggested to result from an autoimmune reaction against the calcium-sensing receptor (CaSR) on parathyroid cells. However, the detection of CaSR antibodies in APS1 remains controversial, with some studies disputing the relevance of the receptor as an autoantigen. OBJECTIVE: The aim of this study was to analyze a defined set of APS1 patient sera for the presence of CaSR antibodies using different assay systems. RESULTS: APS1 patients and individuals with other autoimmune disorders along with healthy subjects were tested for antibody binding to the CaSR. In an immunoprecipitation assay with the CaSR expressed in human embryonic kidney 293 cells, 12 of 14 (85.7%) APS1 and two of 28 (7.1%) Graves' disease patients were considered positive for CaSR antibodies. The prevalence of receptor antibodies was significantly greater than that in the cohort of healthy individuals only in the APS1 patient group (P < 0.0001). In a flow cytometry assay, seven of 14 (50.0%) APS1 patient sera showed binding to the extracellular domain of the CaSR. The prevalence of receptor antibodies in the APS1 patient group was significantly greater than that in the group of healthy controls (P = 0.023). No CaSR antibodies could be detected in any patients or controls using a radiobinding assay. CONCLUSION: The CaSR is an autoantigen in APS1, but detection of antibodies against the receptor appears to be influenced by the assay system used.