Abstract
BackgroundPeripheral nerve injury and bone lesions, well known leprosy complications, lead to deformities and incapacities. The phosphate-regulating gene with homologies to endopeptidase on the X chromosome (PHEX) encodes a homonymous protein (PHEX) implicated in bone metabolism. PHEX/PHEX alterations may result in bone and cartilage lesions. PHEX expression is downregulated by intracellular Mycobacterium leprae (M. leprae) in cultures of human Schwann cells and osteoblasts. M. leprae in vivo effect on PHEX/PHEX is not known.MethodsCross-sectional observational study of 36 leprosy patients (22 lepromatous and 14 borderline-tuberculoid) and 20 healthy volunteers (HV). The following tests were performed: PHEX flow cytometric analysis on blood mononuclear cells, cytokine production in culture supernatant, 25-hydroxyvitamin D (OHvitD) serum levels and 99mTc-MDP three-phase bone scintigraphy, radiography of upper and lower extremities and blood and urine biochemistry.ResultsSignificantly lower PHEX expression levels were observed in lepromatous patients than in the other groups (χ2 = 16.554, p < 0.001 for lymphocytes and χ2 = 13.933, p = 0.001 for monocytes). Low levels of 25-(OHvitD) were observed in HV (median = 23.0 ng/mL) and BT patients (median = 27.5 ng/mL) and normal serum levels were found in LL patients (median = 38.6 ng/mL). Inflammatory cytokines, such as TNF, a PHEX transcription repressor, were lower after stimulation with M. leprae in peripheral blood mononuclear cells from lepromatous in comparison to BT patients and HV (χ2 = 10.820, p < 0.001).ConclusionDownregulation of PHEX may constitute an important early component of bone loss and joint damage in leprosy. The present results suggest a direct effect produced by M. leprae on the osteoarticular system that may use this mechanism.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0651-5) contains supplementary material, which is available to authorized users.
Highlights
Peripheral nerve injury and bone lesions, well known leprosy complications, lead to deformities and incapacities
Ex vivo study: PHEX expression in Peripheral blood mononuclear cells (PBMC) and cytokine production PHEX expression was significantly lower in Lepromatous leprosy (LL) as compared to borderline tuberculoid (BT) patients and healthy volunteers (HV) (Fig. 2) in both monocytes (KW-χ2 = 13,933, p = 0.001) and lymphocytes (KWχ2 = 16,554, p < 0.0001)
Once the downregulation of PHEX expression was observed, we sought to determine the production of inflammatory cytokines by M. leprae-stimulated blood leukocytes
Summary
Peripheral nerve injury and bone lesions, well known leprosy complications, lead to deformities and incapacities. M. leprae in vivo effect on PHEX/PHEX is not known. Bone disease occurs in many clinical conditions, from infectious to metabolic, inflammatory, cancer and genetic disorders. Leprosy, caused by Mycobacterium leprae, is widely known because of. Silva et al J Transl Med (2015) 13:296 of 105 newly-diagnosed adult multibacillary leprosy patients surveyed for up to 8 years after release from treatment, 23 % of the patients were found to have acral resorption [2]. In patients with established disability, bone damage was found to be present in 80 % of patients [3]. M. leprae-filled macrophages can be observed in the medullar cavity and trabecular bone destruction [4]. Different degrees of phalange resorption, bone cysts, trabeculation loss and osteoporosis can be observed in image studies [3, 6]
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