Elsevier

Medical Hypotheses

Volume 81, Issue 1, July 2013, Pages 111-113
Medical Hypotheses

Is primary hyperparathyroidism a pathogenic factor in some conditions mediated by B lymphocytes hyperactivity?

https://doi.org/10.1016/j.mehy.2013.03.044Get rights and content

Abstract

Several clinical cases have shown the association of primary hyperparathyroidism and immune conditions related to B-cell hyperactivity. In some of these cases the treatment of hyperparathyroidism led to the resolution of the autoimmune phenomena. Thus, this paper hypothesizes that high levels of parathyroid hormone (PTH) may modify B lymphocytes function and induce the development of autoimmunity mediated by B-cell hyperactivity.

Introduction

Parathyroid hormone (PTH) is a pleiotropic protein that operates under endocrine, paracrine, autocrine and intracrine mechanisms. Its actions on the immune system are wide and varied, showing both stimulants and repressors effects, depending if the study is conducted either in humans or animals, or according to the type of study (in vivo, ex vivo or in vitro). The underlying comorbidities of patients studied are also determinant factors.

The mechanisms of action of PTH are still elusive more even when there are many possible interactions. The hormone is implicated in different processes such as epithelial-mesenchymal interactions, skeletogenesis and carcinogenesis [1], [2]. In the particular case of its role on the immune system is known that PTH stimulates hematopoiesis and enhances bone marrow engraftment [3], [4] acting directly on various cellular types through specific receptors or indirectly by cytokines such as interleukin-6 (IL-6). Its action in the B lymphocytes is now being investigated and it is premature to elaborate definitive conclusions. A probable pathogenic role of PTH in diverse clinical conditions mediated by B lymphocytes begins to be assumed. By instance, some patients with hyperparathyroidism and gammopathies [5], [6], [7] or autoimmune diseases [8], [9], [10] have shown total recovery of the associated condition after parathyroidectomy.

Section snippets

Activating action of PTH on of the hematopoietic system cells

PTH increases cells of the hematopoietic lineage, including hematopoietic progenitor cells [11]. PTH activates osteoclasts, responsible of bone resorption, through of an indirect via of upregulation of RANK-L in cells of the osteoblast lineage [12]. However the PTH receptor is also expressed by osteoclasts [13], [14]. The anabolic actions of PTH in bone have been suggested to be associated with the differentiation stage of cells in the osteoclast lineage [15]. B and T lymphocytes express PTH

Case reports show the association between autoimmunity and hyperparathyroidism

Several conditions showing hyperparathyroidism and B-cell hyperactivity have been reported. Diverse hematological diseases as chronic lymphocytic leukemia [34], gammapathy of undetermined significance [7], [35], [36], multiple myeloma [37], [38], [39], and autoimmune diseases such as systemic lupus erythematosus [40], antiphospholipid syndrome [41], rheumatoid arthritis [42], celiac disease [43], Sjögreńs syndrome [8], Graves disease [44], [45], myasthenia gravis [46], polymyositis [47], [48]

Hypothesized mechanism for B-cell hyperactivity induced by PTH

PTH may contribute in some cases to the development of autoimmune phenomena in a direct form stimulating T and B lymphocytes through its action with its receptor. In an indirect way the PTH could activate B cells through the induction of IL-6 on stromal/osteoblast cells. This cytokine stimulates B lymphocytes for activation and differentiation into plasmocytes and the subsequent production of antibodies [51], [52]. Additionally, IL-6 is produced and secreted by human parathyroid gland and it is

Consequences of the hypothesis and conclusion

A novel pathogenical factor in autoimmune phenomena is described. The action of PTH on the immune cell may contribute to development of autoimmunity. The observation of cases with both primary hyperparathyroidism and autoimmune diseases are noteworthy. The reverse of autoimmune phenomena after parathyroidectomy should alert us to this event.

In all patients with de novo autoimmune phenomenon, levels of calcium and PTH should be studied because, at least theoretically, a reversible form of

Conflict of interest

None.

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