Hypoparathyroidism is characterized by inappropriately low levels of parathyroid hormone (PTH), leading to hypocalcemia and hyperphosphoremia.
Previous research has highlighted the pivotal role of immune cells in mediating bone effects of PTH, and recent studies have shown a significant increase in infectious diseases in hypoparathyroidism, suggested a possible role for PTH-immune interactions beyond the osteoimmune niche in maintaining immune homeostasis.
Despite the increasing body of evidence on immune derangement in parathyroid disorders, data on the direct effect of PTH on the immune system are scarce.
We recently investigated the immune system in post-surgical hypoparathyroidism in a clinical trial (NCT04059380), discovering significant alterations in patients with inappropriately low levels of PTH. More specifically, patients with hypoparathyroidism had reduced circulating monocytes, CD4+ Lymphocytes, Treg Lymphocytes and CD4+ Naïve Lymphocytes, and increased Natural Killer cells. We also showed the presence of PTH receptor on all immune lineages, and highlighted a decrease in tumor necrosis factor (TNF) and granulocyte-monocyte colony stimulating factor (GM-CSF). Following these findings, the aim of the present study is to further investigate possible alterations in immune response in hypoparathyroidism using flow cytometry analysis of cytokine secretion after in vitro stimulation, and to analyse intracellular calcium mobilization in immune cells in patients and controls, thus evaluating the contribution of altered calcium homeostasis to the increased incidence of infectious diseases in hypoparathyroidism.
The recognition of PTH-immune interactions dates to the 1970s, but until now the generalized effects of PTH on immune response have not been completely elucidated yet. Throughout the last decade, epidemiological studies have highlighted a previously unidentified increase in infectious diseases in patients with hypoparathyroidism, suggesting underlying immune derangement.
The EMPATHY trial was the first study investigating the immune profile in post-surgical hypoparathyroidism, demonstrating many alterations.
However, analysis after in vitro stimulation have not be performed. The aim of the proposed study is to expand our knowledge on the effects of calcium and PTH levels on immunity including intracellular calcium mobilization assessment and response to antigen presentation, in order to deepen our knowledge on the functional aspects of the immune system, comparing patients affected by hypoparathyroidism and controls.