Impaired Immune Function in Patients with Chronic Postsurgical Hypoparathyroidism: Results of the EMPATHY Study.

Context despite the pivotal role of calcium signaling in immune response, little is known about immune function in patients affected by hypoparathyroidism. Objective to evaluate immune function in hypoparathyroidism. Design The Evaluation of iMmune function in Postsurgical and AuToimmune HYpoparathyroidism (NCT04059380) is a case-control cross-sectional study. Setting Italian referral center. Patients 20 patients with postsurgical hypoparathyroidism (12 females) and 20 age- and sex-matched controls. Main outcome measure(s) calcium metabolism assessment, PBMC profiling via flow cytometry, PTH receptor 1 (PTHr1) expression analysis using immunofluorescence and PrimeFlow RNA assay, gene expression analysis via real-time PCR, cytokine measurement, and evaluation of infectious disease frequency and severity. Results immune cell profiling revealed decreased monocytes, regulatory, naive and total CD4 + T lymphocytes, which correlated with total calcium, ionized calcium, and PTH levels, in patients with hypoparathyroidism. Patients with hypoparathyroidism had higher CD3 -CD56 + natural killer (NK) cell count, which inversely correlated with calcium, PTH, and vitamin D levels. Furthermore, they exhibited decreased TNF and GM-CSF gene expression and decreased circulating TNF levels. Gene expression and immunofluorescence analysis confirmed PTHr1 expression in all PBMC lineages; however, the percentage of cells expressing PTHr1 was lower while the intensity of PTHr1 expression in monocytes, total T lymphocytes, CD8 +CD4 + and CD4 + T lymphocytes, and total NK cells were higher in patients with hypoparathyroidism. Conclusions this study describes for the first time the immune alterations in patients with hypoparathyroidism receiving conventional therapies, supporting the immunoregulatory role of PTH and proposing an explanation for the increased susceptibility to infections observed in epidemiological studies.