Downregulation of PHEX in multibacillary leprosy patients: observational cross-sectional study

Journal of Translational Medicine

Research

Sandra R. Boiça Silva¹  Antonio J. Tempone²  Pedro H. L. Silva³  José A. C. Nery³  Ximena Illarramendi³  Euzenir N. Sarno³  Danuza Esquenazi⁴  Maria Cristina V. Pessolani⁵  Geraldo M. B. Pereira⁶  Edson Boasquevisque⁷  Alexandra M. V. Monteiro⁷ 

[1] Disciplina de Patologia Geral e Laboratório de Imunopatologia, Departamento de Patologia e Laboratórios, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro (UERJ), Av Professor Manuel de Abreu 444, Vila Isabel, 20550-170, Rio de Janeiro, RJ, Brazil;Laboratório de Biologia Molecular de Parasitas e Vetores, Instituto Oswaldo Cruz (IOC) – Oswaldo Cruz Foundation (FIOCRUZ), Av. Brasil 4365, Manguinhos, 21040-360, Rio de Janeiro, RJ, Brazil;Laboratório de Hanseníase, Instituto Oswaldo Cruz (IOC) – Oswaldo Cruz Foundation (FIOCRUZ), Av. Brasil 4365, Manguinhos, 21040-360, Rio de Janeiro, RJ, Brazil;Laboratório de Hanseníase, Instituto Oswaldo Cruz (IOC) – Oswaldo Cruz Foundation (FIOCRUZ), Av. Brasil 4365, Manguinhos, 21040-360, Rio de Janeiro, RJ, Brazil;Disciplina de Patologia Geral e Laboratório de Imunopatologia, Departamento de Patologia e Laboratórios, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro (UERJ), Av Professor Manuel de Abreu 444, Vila Isabel, 20550-170, Rio de Janeiro, RJ, Brazil;Laboratório de Microbiologia Celular, Instituto Oswaldo Cruz (IOC) – Oswaldo Cruz Foundation (FIOCRUZ), Av. Brasil 4365, Manguinhos, 21040-360, Rio de Janeiro, RJ, Brazil;Laboratório de Microbiologia Celular, Instituto Oswaldo Cruz (IOC) – Oswaldo Cruz Foundation (FIOCRUZ), Av. Brasil 4365, Manguinhos, 21040-360, Rio de Janeiro, RJ, Brazil;Disciplina de Patologia Geral e Laboratório de Imunopatologia, Departamento de Patologia e Laboratórios, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro (UERJ), Av Professor Manuel de Abreu 444, Vila Isabel, 20550-170, Rio de Janeiro, RJ, Brazil;Serviço de Medicina Nuclear, Departamento de Radiologia, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro (UERJ), Av. Prof. Manuel de Abreu 444, Vila Isabel, 20550-170, Rio de Janeiro, RJ, Brazil;

关键词: PHEX;    Mycobacterium leprae;    Leprosy;    Vitamin D;    Bone damage;    Inflammatory cytokines;   

DOI  :  10.1186/s12967-015-0651-5

 received in 2015-06-20, accepted in 2015-08-25,  发布年份 2015

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© Silva et al. 2015