| Author | Silva, Sandra R. Boiça | |
| Author | Illarramendi Rojas, Ximena | |
| Author | Tempone, Antonio J. | |
| Author | Silva, Pedro H. L. | |
| Author | Nery, José A. C. | |
| Author | Monteiro, Alexandra M. V. | |
| Author | Pessolani, Maria Cristina V. | |
| Author | Boasquevisque, Edson | |
| Author | Sarno, Euzenir N. | |
| Author | Pereira, Geraldo M. B. | |
| Author | Esquenazi, Danuza | |
| Access date | 2016-03-17T16:57:22Z | |
| Available date | 2016-03-17T16:57:22Z | |
| Document date | 2015 | |
| Citation | SILVA, Sandra R. Boiça et al. Downregulation of PHEX in multibacillary leprosy patients: observational cross-sectional study. Journal of Translational Medicine, v.13:296, 8p, 2015. | pt_BR |
| ISSN | 1479-5876 | |
| URI | https://www.arca.fiocruz.br/handle/icict/13203 | |
| Language | eng | pt_BR |
| Publisher | BioMed Central | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Vitamina D | pt_BR |
| Subject in Portuguese | Mycobacterium leprae | pt_BR |
| Subject in Portuguese | Hanseníase | pt_BR |
| Subject in Portuguese | Dano nos ossos | pt_BR |
| Subject in Portuguese | Endopeptidase Neutra Reguladora de Fosfato PHEX | pt_BR |
| Title | Downregulation of PHEX in multibacillary leprosy patients: observational cross-sectional study | pt_BR |
| Type | Article | |
| DOI | 10.1186/s12967-015-0651-5 | |
| Abstract | Background: Peripheral 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.
Methods: Cross-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.
Results: Significantly 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).
Conclusion: Downregulation 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. | pt_BR |
| Affilliation | Universidade do Estado do Rio de Janeiro (UERJ). Faculdade de Ciências Médicas. Departamento de Patologia e Laboratórios. Disciplina de Patologia Geral e Laboratório de Imunopatologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular de Parasitas e Vetores. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade do Estado do Rio de Janeiro (UERJ). Faculdade de Ciências Médicas. Departamento de Radiologia. Serviço de Medicina Nuclear. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil | pt_BR |
| Affilliation | Universidade do Estado do Rio de Janeiro (UERJ). Faculdade de Ciências Médicas. Departamento de Radiologia. Serviço de Medicina Nuclear. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil / Universidade do Estado do Rio de Janeiro (UERJ). Faculdade de Ciências Médicas. Departamento de Patologia e Laboratórios. Disciplina de Patologia Geral e Laboratório de Imunopatologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil / Universidade do Estado do Rio de Janeiro (UERJ). Faculdade de Ciências Médicas. Departamento de Patologia e Laboratórios. Disciplina de Patologia Geral e Laboratório de Imunopatologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | PHEX | pt_BR |
| Subject | Mycobacterium leprae | pt_BR |
| Subject | Leprosy | pt_BR |
| Subject | Vitamin D | pt_BR |
| Subject | Bone damage | pt_BR |
| Subject | Inflammatory cytokines | pt_BR |
