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Euzenir Nunes Sarno - One of the best experts on this subject based on the ideXlab platform.
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Autophagy Impairment Is Associated With Increased Inflammasome Activation and Reversal Reaction Development in Multibacillary Leprosy.
Frontiers in immunology, 2018Co-Authors: Mayara Garcia De Mattos Barbosa, Jose Augusto Da Costa Nery, Bruno Jorge De Andrade Silva, Tayná Quintella Assis, Rhana Berto Da Silva Prata, Helen Ferreira, Priscila Ribeiro Andrade, Jéssica Araújo Da Paixão De Oliveira, Gilberto Marcelo Sperandio Da Silva, Euzenir Nunes SarnoAbstract:Leprosy reactions are responsible for incapacities in Leprosy and represent the major cause of permanent neuropathy. The identification of biomarkers able to identify patients more prone to develop reaction could contribute to adequate clinical management and the prevention of disability. Reversal reaction may occur in unstable borderline patients and also in lepromatous patients. To identify biomarker signature profiles related with the reversal reaction onset, Multibacillary patients were recruited and classified accordingly the occurrence or not of reversal reaction during or after multidrugtherapy. Analysis of skin lesion cells at diagnosis of Multibacillary Leprosy demonstrated that in the group that developed reaction (T1R) in the future there was a downregulation of autophagy associated with the overexpression of TLR2 and MLST8. The autophagy impairment in T1R group was associated with increased expression of NLRP3, caspase-1 (p10) and IL-1β production. In addition, analysis of IL-1β production in serum from Multibacillary patients demonstrated that patients who developed reversal reaction have significantly increased concentrations of IL-1β at diagnosis, suggesting that the pattern of innate immune responses could predict the reactional episode outcome. In vitro analysis demonstrated that the blockade of autophagy with 3-methyladenine (3-MA) in Mycobacterium leprae-stimulated human primary monocytes increased the assembly of NLRP3 specks assembly, and it was associated with an increase of IL-1β and IL-6 production. Together, our data suggest an important role for autophagy in Multibacillary Leprosy patients to avoid exacerbated inflammasome activation and the onset of reversal reaction.
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image_2_Autophagy Impairment Is Associated With Increased Inflammasome Activation and Reversal Reaction Development in Multibacillary Leprosy.JPEG
2018Co-Authors: Mayara Garcia De Mattos Barbosa, Jose Augusto Da Costa Nery, Bruno Jorge De Andrade Silva, Tayná Quintella Assis, Rhana Berto Da Silva Prata, Helen Ferreira, Priscila Ribeiro Andrade, Jéssica Araújo Da Paixão De Oliveira, Gilberto Marcelo Sperandio Da Silva, Euzenir Nunes SarnoAbstract:Leprosy reactions are responsible for incapacities in Leprosy and represent the major cause of permanent neuropathy. The identification of biomarkers able to identify patients more prone to develop reaction could contribute to adequate clinical management and the prevention of disability. Reversal reaction may occur in unstable borderline patients and also in lepromatous patients. To identify biomarker signature profiles related with the reversal reaction onset, Multibacillary patients were recruited and classified accordingly the occurrence or not of reversal reaction during or after multidrugtherapy. Analysis of skin lesion cells at diagnosis of Multibacillary Leprosy demonstrated that in the group that developed reaction (T1R) in the future there was a downregulation of autophagy associated with the overexpression of TLR2 and MLST8. The autophagy impairment in T1R group was associated with increased expression of NLRP3, caspase-1 (p10) and IL-1β production. In addition, analysis of IL-1β production in serum from Multibacillary patients demonstrated that patients who developed reversal reaction have significantly increased concentrations of IL-1β at diagnosis, suggesting that the pattern of innate immune responses could predict the reactional episode outcome. In vitro analysis demonstrated that the blockade of autophagy with 3-methyladenine (3-MA) in Mycobacterium leprae-stimulated human primary monocytes increased the assembly of NLRP3 specks assembly, and it was associated with an increase of IL-1β and IL-6 production. Together, our data suggest an important role for autophagy in Multibacillary Leprosy patients to avoid exacerbated inflammasome activation and the onset of reversal reaction.
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table_1_Autophagy Impairment Is Associated With Increased Inflammasome Activation and Reversal Reaction Development in Multibacillary Leprosy.XLSX
2018Co-Authors: Mayara Garcia De Mattos Barbosa, Jose Augusto Da Costa Nery, Bruno Jorge De Andrade Silva, Tayná Quintella Assis, Rhana Berto Da Silva Prata, Helen Ferreira, Priscila Ribeiro Andrade, Jéssica Araújo Da Paixão De Oliveira, Gilberto Marcelo Sperandio Da Silva, Euzenir Nunes SarnoAbstract:Leprosy reactions are responsible for incapacities in Leprosy and represent the major cause of permanent neuropathy. The identification of biomarkers able to identify patients more prone to develop reaction could contribute to adequate clinical management and the prevention of disability. Reversal reaction may occur in unstable borderline patients and also in lepromatous patients. To identify biomarker signature profiles related with the reversal reaction onset, Multibacillary patients were recruited and classified accordingly the occurrence or not of reversal reaction during or after multidrugtherapy. Analysis of skin lesion cells at diagnosis of Multibacillary Leprosy demonstrated that in the group that developed reaction (T1R) in the future there was a downregulation of autophagy associated with the overexpression of TLR2 and MLST8. The autophagy impairment in T1R group was associated with increased expression of NLRP3, caspase-1 (p10) and IL-1β production. In addition, analysis of IL-1β production in serum from Multibacillary patients demonstrated that patients who developed reversal reaction have significantly increased concentrations of IL-1β at diagnosis, suggesting that the pattern of innate immune responses could predict the reactional episode outcome. In vitro analysis demonstrated that the blockade of autophagy with 3-methyladenine (3-MA) in Mycobacterium leprae-stimulated human primary monocytes increased the assembly of NLRP3 specks assembly, and it was associated with an increase of IL-1β and IL-6 production. Together, our data suggest an important role for autophagy in Multibacillary Leprosy patients to avoid exacerbated inflammasome activation and the onset of reversal reaction.
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image_1_Autophagy Impairment Is Associated With Increased Inflammasome Activation and Reversal Reaction Development in Multibacillary Leprosy.TIF
2018Co-Authors: Mayara Garcia De Mattos Barbosa, Jose Augusto Da Costa Nery, Bruno Jorge De Andrade Silva, Tayná Quintella Assis, Rhana Berto Da Silva Prata, Helen Ferreira, Priscila Ribeiro Andrade, Jéssica Araújo Da Paixão De Oliveira, Gilberto Marcelo Sperandio Da Silva, Euzenir Nunes SarnoAbstract:Leprosy reactions are responsible for incapacities in Leprosy and represent the major cause of permanent neuropathy. The identification of biomarkers able to identify patients more prone to develop reaction could contribute to adequate clinical management and the prevention of disability. Reversal reaction may occur in unstable borderline patients and also in lepromatous patients. To identify biomarker signature profiles related with the reversal reaction onset, Multibacillary patients were recruited and classified accordingly the occurrence or not of reversal reaction during or after multidrugtherapy. Analysis of skin lesion cells at diagnosis of Multibacillary Leprosy demonstrated that in the group that developed reaction (T1R) in the future there was a downregulation of autophagy associated with the overexpression of TLR2 and MLST8. The autophagy impairment in T1R group was associated with increased expression of NLRP3, caspase-1 (p10) and IL-1β production. In addition, analysis of IL-1β production in serum from Multibacillary patients demonstrated that patients who developed reversal reaction have significantly increased concentrations of IL-1β at diagnosis, suggesting that the pattern of innate immune responses could predict the reactional episode outcome. In vitro analysis demonstrated that the blockade of autophagy with 3-methyladenine (3-MA) in Mycobacterium leprae-stimulated human primary monocytes increased the assembly of NLRP3 specks assembly, and it was associated with an increase of IL-1β and IL-6 production. Together, our data suggest an important role for autophagy in Multibacillary Leprosy patients to avoid exacerbated inflammasome activation and the onset of reversal reaction.
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Multibacillary Leprosy by population groups in brazil lessons from an observational study
PLOS Neglected Tropical Diseases, 2017Co-Authors: Ximena Illarramendi, Jose Augusto Da Costa Nery, Mauricio Lisboa Nobre, Kathryn M Dupnik, Mariana A Hacker, Selma M B Jeronimo, Euzenir Nunes SarnoAbstract:Leprosy remains an important public health problem in Brazil where 28,761 new cases were diagnosed in 2015, the second highest number of new cases detected globally. The disease is caused by Mycobacterium leprae, a pathogen spread by patients with Multibacillary (MB) Leprosy. This study was designed to identify population groups most at risk for MB disease in Brazil, contributing to new ideas for early diagnosis and Leprosy control. Methods: A national databank of cases reported in Brazil (2001–2013) was used to evaluate epidemiological characteristics of MB Leprosy. Additionally, the databank of a Leprosy reference center was used to determine factors associated with higher bacillary loads. Results: A total of 541,090 cases were analyzed. New case detection rates (NCDRs) increased with age, especially for men with MB Leprosy, reaching 44.8 new cases/100,000 population in 65–69 year olds. Males and subjects older than 59 years had twice the odds of MB Leprosy than females and younger cases (OR = 2.36, CI95% = 2.33–2.38; OR = 1.99, CI95% = 1.96–2.02, respectively). Bacillary load was higher in male and in patients aged 20–39 and 40–59 years compared to females and other age groups. From 2003 to 2013, there was a progressive reduction in annual NCDRs and an increase in the percentage of MB cases and of elderly patients in Brazil. These data suggest reduction of Leprosy transmission in the country. Conclusion: Public health policies for Leprosy control in endemic areas in Brazil should include activities especially addressed to men and to the elderly in order to further reduce M. leprae transmission.
Jose Augusto Da Costa Nery - One of the best experts on this subject based on the ideXlab platform.
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Autophagy Impairment Is Associated With Increased Inflammasome Activation and Reversal Reaction Development in Multibacillary Leprosy.
Frontiers in immunology, 2018Co-Authors: Mayara Garcia De Mattos Barbosa, Jose Augusto Da Costa Nery, Bruno Jorge De Andrade Silva, Tayná Quintella Assis, Rhana Berto Da Silva Prata, Helen Ferreira, Priscila Ribeiro Andrade, Jéssica Araújo Da Paixão De Oliveira, Gilberto Marcelo Sperandio Da Silva, Euzenir Nunes SarnoAbstract:Leprosy reactions are responsible for incapacities in Leprosy and represent the major cause of permanent neuropathy. The identification of biomarkers able to identify patients more prone to develop reaction could contribute to adequate clinical management and the prevention of disability. Reversal reaction may occur in unstable borderline patients and also in lepromatous patients. To identify biomarker signature profiles related with the reversal reaction onset, Multibacillary patients were recruited and classified accordingly the occurrence or not of reversal reaction during or after multidrugtherapy. Analysis of skin lesion cells at diagnosis of Multibacillary Leprosy demonstrated that in the group that developed reaction (T1R) in the future there was a downregulation of autophagy associated with the overexpression of TLR2 and MLST8. The autophagy impairment in T1R group was associated with increased expression of NLRP3, caspase-1 (p10) and IL-1β production. In addition, analysis of IL-1β production in serum from Multibacillary patients demonstrated that patients who developed reversal reaction have significantly increased concentrations of IL-1β at diagnosis, suggesting that the pattern of innate immune responses could predict the reactional episode outcome. In vitro analysis demonstrated that the blockade of autophagy with 3-methyladenine (3-MA) in Mycobacterium leprae-stimulated human primary monocytes increased the assembly of NLRP3 specks assembly, and it was associated with an increase of IL-1β and IL-6 production. Together, our data suggest an important role for autophagy in Multibacillary Leprosy patients to avoid exacerbated inflammasome activation and the onset of reversal reaction.
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Blood coagulation abnormalities in Multibacillary Leprosy patients
2018Co-Authors: Débora Santos Da Silva, Lisandra Antonia Castro Teixeira, Daniela Gois Beghini, André Teixeira Da Silva Ferreira, Márcia De Berredo Moreira Pinho, Patricia Sammarco Rosa, Marli Rambaldi Ribeiro, Monica Di Calafiori Freire, Mariana Andrea Hacker, Jose Augusto Da Costa NeryAbstract:BackgroundLeprosy is a chronic dermato-neurological disease caused by Mycobacterium leprae infection. In 2016, more than 200,000 new cases of Leprosy were detected around the world, representing the most frequent cause of infectious irreversible deformities and disabilities.Principal findingsIn the present work, we demonstrate a consistent procoagulant profile on 40 reactional and non-reactional Multibacillary Leprosy patients. A retrospective analysis in search of signs of coagulation abnormalities among 638 Leprosy patients identified 35 Leprosy patients (5.48%) which displayed a characteristic lipid-like clot formed between blood clot and serum during serum harvesting, herein named ‘leprosum clot’. Most of these patients (n = 16, 45.7%) belonged to the lepromatous Leprosy pole of the disease. In addition, formation of the leprosum clot was directly correlated with increased plasma levels of soluble tissue factor and von Willebrand factor. High performance thin layer chromatography demonstrated a high content of neutral lipids in the leprosum clot, and proteomic analysis demonstrated that the leprosum clot presented in these patients is highly enriched in fibrin. Remarkably, differential 2D-proteomics analysis between leprosum clots and control clots identified two proteins present only in Leprosy patients clots: complement component 3 and 4 and inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP). In agreement with those observations we demonstrated that M. leprae induces hepatocytes release of IHRP in vitro.ConclusionsWe demonstrated that Leprosy MB patients develop a procoagulant status due to high levels of plasmatic fibrinogen, anti-cardiolipin antibodies, von Willebrand factor and soluble tissue factor. We propose that some of these components, fibrinogen for example, presents potential as predictive biomarkers of Leprosy reactions, generating tools for earlier diagnosis and treatment of these events.
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image_2_Autophagy Impairment Is Associated With Increased Inflammasome Activation and Reversal Reaction Development in Multibacillary Leprosy.JPEG
2018Co-Authors: Mayara Garcia De Mattos Barbosa, Jose Augusto Da Costa Nery, Bruno Jorge De Andrade Silva, Tayná Quintella Assis, Rhana Berto Da Silva Prata, Helen Ferreira, Priscila Ribeiro Andrade, Jéssica Araújo Da Paixão De Oliveira, Gilberto Marcelo Sperandio Da Silva, Euzenir Nunes SarnoAbstract:Leprosy reactions are responsible for incapacities in Leprosy and represent the major cause of permanent neuropathy. The identification of biomarkers able to identify patients more prone to develop reaction could contribute to adequate clinical management and the prevention of disability. Reversal reaction may occur in unstable borderline patients and also in lepromatous patients. To identify biomarker signature profiles related with the reversal reaction onset, Multibacillary patients were recruited and classified accordingly the occurrence or not of reversal reaction during or after multidrugtherapy. Analysis of skin lesion cells at diagnosis of Multibacillary Leprosy demonstrated that in the group that developed reaction (T1R) in the future there was a downregulation of autophagy associated with the overexpression of TLR2 and MLST8. The autophagy impairment in T1R group was associated with increased expression of NLRP3, caspase-1 (p10) and IL-1β production. In addition, analysis of IL-1β production in serum from Multibacillary patients demonstrated that patients who developed reversal reaction have significantly increased concentrations of IL-1β at diagnosis, suggesting that the pattern of innate immune responses could predict the reactional episode outcome. In vitro analysis demonstrated that the blockade of autophagy with 3-methyladenine (3-MA) in Mycobacterium leprae-stimulated human primary monocytes increased the assembly of NLRP3 specks assembly, and it was associated with an increase of IL-1β and IL-6 production. Together, our data suggest an important role for autophagy in Multibacillary Leprosy patients to avoid exacerbated inflammasome activation and the onset of reversal reaction.
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table_1_Autophagy Impairment Is Associated With Increased Inflammasome Activation and Reversal Reaction Development in Multibacillary Leprosy.XLSX
2018Co-Authors: Mayara Garcia De Mattos Barbosa, Jose Augusto Da Costa Nery, Bruno Jorge De Andrade Silva, Tayná Quintella Assis, Rhana Berto Da Silva Prata, Helen Ferreira, Priscila Ribeiro Andrade, Jéssica Araújo Da Paixão De Oliveira, Gilberto Marcelo Sperandio Da Silva, Euzenir Nunes SarnoAbstract:Leprosy reactions are responsible for incapacities in Leprosy and represent the major cause of permanent neuropathy. The identification of biomarkers able to identify patients more prone to develop reaction could contribute to adequate clinical management and the prevention of disability. Reversal reaction may occur in unstable borderline patients and also in lepromatous patients. To identify biomarker signature profiles related with the reversal reaction onset, Multibacillary patients were recruited and classified accordingly the occurrence or not of reversal reaction during or after multidrugtherapy. Analysis of skin lesion cells at diagnosis of Multibacillary Leprosy demonstrated that in the group that developed reaction (T1R) in the future there was a downregulation of autophagy associated with the overexpression of TLR2 and MLST8. The autophagy impairment in T1R group was associated with increased expression of NLRP3, caspase-1 (p10) and IL-1β production. In addition, analysis of IL-1β production in serum from Multibacillary patients demonstrated that patients who developed reversal reaction have significantly increased concentrations of IL-1β at diagnosis, suggesting that the pattern of innate immune responses could predict the reactional episode outcome. In vitro analysis demonstrated that the blockade of autophagy with 3-methyladenine (3-MA) in Mycobacterium leprae-stimulated human primary monocytes increased the assembly of NLRP3 specks assembly, and it was associated with an increase of IL-1β and IL-6 production. Together, our data suggest an important role for autophagy in Multibacillary Leprosy patients to avoid exacerbated inflammasome activation and the onset of reversal reaction.
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image_1_Autophagy Impairment Is Associated With Increased Inflammasome Activation and Reversal Reaction Development in Multibacillary Leprosy.TIF
2018Co-Authors: Mayara Garcia De Mattos Barbosa, Jose Augusto Da Costa Nery, Bruno Jorge De Andrade Silva, Tayná Quintella Assis, Rhana Berto Da Silva Prata, Helen Ferreira, Priscila Ribeiro Andrade, Jéssica Araújo Da Paixão De Oliveira, Gilberto Marcelo Sperandio Da Silva, Euzenir Nunes SarnoAbstract:Leprosy reactions are responsible for incapacities in Leprosy and represent the major cause of permanent neuropathy. The identification of biomarkers able to identify patients more prone to develop reaction could contribute to adequate clinical management and the prevention of disability. Reversal reaction may occur in unstable borderline patients and also in lepromatous patients. To identify biomarker signature profiles related with the reversal reaction onset, Multibacillary patients were recruited and classified accordingly the occurrence or not of reversal reaction during or after multidrugtherapy. Analysis of skin lesion cells at diagnosis of Multibacillary Leprosy demonstrated that in the group that developed reaction (T1R) in the future there was a downregulation of autophagy associated with the overexpression of TLR2 and MLST8. The autophagy impairment in T1R group was associated with increased expression of NLRP3, caspase-1 (p10) and IL-1β production. In addition, analysis of IL-1β production in serum from Multibacillary patients demonstrated that patients who developed reversal reaction have significantly increased concentrations of IL-1β at diagnosis, suggesting that the pattern of innate immune responses could predict the reactional episode outcome. In vitro analysis demonstrated that the blockade of autophagy with 3-methyladenine (3-MA) in Mycobacterium leprae-stimulated human primary monocytes increased the assembly of NLRP3 specks assembly, and it was associated with an increase of IL-1β and IL-6 production. Together, our data suggest an important role for autophagy in Multibacillary Leprosy patients to avoid exacerbated inflammasome activation and the onset of reversal reaction.
Geraldo M B Pereira - One of the best experts on this subject based on the ideXlab platform.
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downregulation of phex in Multibacillary Leprosy patients observational cross sectional study
Journal of Translational Medicine, 2015Co-Authors: Sandra Boica R Silva, Ximena Illarramendi, Antonio Jorge Tempone, Pedro Henrique Lopes Da Silva, Jose Augusto Da Costa Nery, Alexandra Maria Vieira Monteiro, Maria Cristina Vidal Pessolani, Edson Boasquevisque, Euzenir Nunes Sarno, Geraldo M B PereiraAbstract: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.
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downregulation of phex in Multibacillary Leprosy patients observational cross sectional study
Journal of Translational Medicine, 2015Co-Authors: Sandra Boica R Silva, Ximena Illarramendi, Antonio Jorge Tempone, Pedro Henrique Lopes Da Silva, Jose Augusto Da Costa Nery, Maria Cristina Vidal Pessolani, Edson Boasquevisque, Euzenir Nunes Sarno, Alexandra Monteiro, Geraldo M B PereiraAbstract: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. 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. 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). 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.
Ximena Illarramendi - One of the best experts on this subject based on the ideXlab platform.
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Multibacillary Leprosy by population groups in brazil lessons from an observational study
PLOS Neglected Tropical Diseases, 2017Co-Authors: Ximena Illarramendi, Jose Augusto Da Costa Nery, Mauricio Lisboa Nobre, Kathryn M Dupnik, Mariana A Hacker, Selma M B Jeronimo, Euzenir Nunes SarnoAbstract:Leprosy remains an important public health problem in Brazil where 28,761 new cases were diagnosed in 2015, the second highest number of new cases detected globally. The disease is caused by Mycobacterium leprae, a pathogen spread by patients with Multibacillary (MB) Leprosy. This study was designed to identify population groups most at risk for MB disease in Brazil, contributing to new ideas for early diagnosis and Leprosy control. Methods: A national databank of cases reported in Brazil (2001–2013) was used to evaluate epidemiological characteristics of MB Leprosy. Additionally, the databank of a Leprosy reference center was used to determine factors associated with higher bacillary loads. Results: A total of 541,090 cases were analyzed. New case detection rates (NCDRs) increased with age, especially for men with MB Leprosy, reaching 44.8 new cases/100,000 population in 65–69 year olds. Males and subjects older than 59 years had twice the odds of MB Leprosy than females and younger cases (OR = 2.36, CI95% = 2.33–2.38; OR = 1.99, CI95% = 1.96–2.02, respectively). Bacillary load was higher in male and in patients aged 20–39 and 40–59 years compared to females and other age groups. From 2003 to 2013, there was a progressive reduction in annual NCDRs and an increase in the percentage of MB cases and of elderly patients in Brazil. These data suggest reduction of Leprosy transmission in the country. Conclusion: Public health policies for Leprosy control in endemic areas in Brazil should include activities especially addressed to men and to the elderly in order to further reduce M. leprae transmission.
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downregulation of phex in Multibacillary Leprosy patients observational cross sectional study
Journal of Translational Medicine, 2015Co-Authors: Sandra Boica R Silva, Ximena Illarramendi, Antonio Jorge Tempone, Pedro Henrique Lopes Da Silva, Jose Augusto Da Costa Nery, Alexandra Maria Vieira Monteiro, Maria Cristina Vidal Pessolani, Edson Boasquevisque, Euzenir Nunes Sarno, Geraldo M B PereiraAbstract: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.
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downregulation of phex in Multibacillary Leprosy patients observational cross sectional study
Journal of Translational Medicine, 2015Co-Authors: Sandra Boica R Silva, Ximena Illarramendi, Antonio Jorge Tempone, Pedro Henrique Lopes Da Silva, Jose Augusto Da Costa Nery, Maria Cristina Vidal Pessolani, Edson Boasquevisque, Euzenir Nunes Sarno, Alexandra Monteiro, Geraldo M B PereiraAbstract: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. 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. 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). 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.
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progression of acral bone resorption in Multibacillary Leprosy
Acta leprologica, 2000Co-Authors: Ximena Illarramendi, E Carregal, J A C Nery, E N SarnoAbstract:Bien que depuis l'application de la strategie globale d'elimination de la lepre preconisee par l'OMS la maladie soit devenue curable, deformations et mutilations restent frequemment observees dans les pays d'endemie. Il est donc important d'evaluer l'incidence et les facteurs de risque des resorptions osseuses survenant sous polychimiotherapie (PCT) antibacillaire. 105 nouveaux patients multibacillaires depistes entre 1990 et 1992 ont ete surveilles jusqu'en 1999. A cette date, 23 % des patients avaient des signes de resorption osseuse et une progression du processus a ete notee plus de huit ans apres l'arret de la PCT. Les facteurs de risque retrouves ont ete : le sexe masculin, le grade d'invalidite et l'existence de deformations au moment du diagnostic, et la survenue de quatre episodes reactionnels ou plus. La surveillance des patients a risque apres arret de traitement apparait donc indispensable.
Sandra Boica R Silva - One of the best experts on this subject based on the ideXlab platform.
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downregulation of phex in Multibacillary Leprosy patients observational cross sectional study
Journal of Translational Medicine, 2015Co-Authors: Sandra Boica R Silva, Ximena Illarramendi, Antonio Jorge Tempone, Pedro Henrique Lopes Da Silva, Jose Augusto Da Costa Nery, Alexandra Maria Vieira Monteiro, Maria Cristina Vidal Pessolani, Edson Boasquevisque, Euzenir Nunes Sarno, Geraldo M B PereiraAbstract: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.
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downregulation of phex in Multibacillary Leprosy patients observational cross sectional study
Journal of Translational Medicine, 2015Co-Authors: Sandra Boica R Silva, Ximena Illarramendi, Antonio Jorge Tempone, Pedro Henrique Lopes Da Silva, Jose Augusto Da Costa Nery, Maria Cristina Vidal Pessolani, Edson Boasquevisque, Euzenir Nunes Sarno, Alexandra Monteiro, Geraldo M B PereiraAbstract: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. 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. 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). 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.