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ContextDespite the pivotal role of calcium signaling in immune response, little is known about immune function in patients affected by hypoparathyroidism.ObjectiveThis work aimed to evaluate immune function in hypoparathyroidism.MethodsThe Evaluation of iMmune function in Postsurgical and AuToimmune HYpoparathyroidism (NCT04059380) is a case-control, cross-sectional study set in an Italian referral center. Participants included 20 patients with postsurgical hypoparathyroidism (12 females) and 20 age- and sex-matched controls. Main outcome measures included calcium metabolism assessment, peripheral blood mononuclear cells (PBMC) profiling via flow cytometry, parathyroid hormone receptor 1 (PTHr1) expression analysis using immunofluorescence and PrimeFlow RNA assay, gene expression analysis via real-time polymerase chain reaction, cytokine measurement, and evaluation of infectious disease frequency and severity.ResultsImmune 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 a higher CD3-CD56+ natural killer (NK) cell count, which inversely correlated with calcium, PTH, and vitamin D levels. Furthermore, they exhibited decreased tumor necrosis factor (TNF) and granulocyte-macrophage colony-stimulating factor 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, whereas the intensity of PTHr1 expression in monocytes, total T lymphocytes, CD8+CD4+ and CD4+ T lymphocytes, and total NK cells was higher in patients with hypoparathyroidism.ConclusionsThis 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.

Original publication

DOI

10.1210/clinem/dgab038

Type

Journal article

Journal

The Journal of clinical endocrinology and metabolism

Publication Date

04/2021

Volume

106

Pages

e2215 - e2227

Addresses

Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.

Keywords

Leukocytes, Mononuclear, CD4-Positive T-Lymphocytes, Immune System, Humans, Hypoparathyroidism, Immune System Diseases, Chronic Disease, Postoperative Complications, Calcium, Parathyroid Hormone, Receptor, Parathyroid Hormone, Type 1, Parathyroidectomy, Case-Control Studies, Cross-Sectional Studies, Pilot Projects, Autoimmunity, Adult, Aged, Middle Aged, Italy, Female, Male