The Experts below are selected from a list of 294 Experts worldwide ranked by ideXlab platform
Diana N. J. Lockwood - One of the best experts on this subject based on the ideXlab platform.
-
tumour necrosis factor alpha tnf α synthesis is associated with the skin and peripheral nerve pathology of leprosy Reversal Reactions
Clinical and Experimental Immunology, 2008Co-Authors: S Khanolkaryoung, N B Rayment, Paul M Brickell, David R Katz, S Vinayakumar, M J Colston, Diana N. J. LockwoodAbstract:SUMMARY Leprosy may be complicated by episodes of increased cell-mediated imtnunity tovk'ards Myco-bacterium leprae (Reversal Reactions) which result in severe local immunopathology in skin lesionsand peripheral nerves. Using in situ hybridization and MoAb techniques we have demonstratedTNF-a mRNA and TNF-o protein in macrophages infiltrating leprosy skin and peripheral nerve.Levels of TNF-Q mRNA are significantly increased in Reactional skin and nerve, particularly inborderline tubercuioid patients. TNF-o mRNA and TNF-Q protein levels are higher in Reactionalnerves then Reactional skin. In both Reactional skin and nerve TNF-a mRNA is more abundantthan TNF-a protein; this may reflect the rapid turnover of TNF-o protein in an immunologicallydynamic situation, such as is seen in Reversal Reaction. Our findings emphasize the importance ofdocumenting both mRNA and protein production when assessing the role of eytokines inpathology. The leprosy Reversal Reaction may be regarded as a useful model of tissue immuno-patbology in which TNF-a is generated as part of the host response to infection, but also produceslocal tissue damage.Keywords leprosy Reversal Reaction TNF In situ hybridization nerve damage
-
tumour necrosis factor alpha tnf α synthesis is associated with the skin and peripheral nerve pathology of leprosy Reversal Reactions
Clinical and Experimental Immunology, 2008Co-Authors: S Khanolkaryoung, N B Rayment, Paul M Brickell, David R Katz, S Vinayakumar, M J Colston, Diana N. J. LockwoodAbstract:Leprosy may be complicated by episodes of increased cell-mediated immunity towards Mycobacterium leprae (Reversal Reactions) which result in severe local immunopathology in skin lesions and peripheral nerves. Using in situ hybridization and MoAb techniques we have demonstrated TNF-alpha mRNA and TNF-alpha protein in macrophages infiltrating leprosy skin and peripheral nerve. Levels of TNF-alpha mRNA are significantly increased in Reactional skin and nerve, particularly in borderline tuberculoid patients. TNF-alpha mRNA and TNF-alpha protein levels are higher in Reactional nerves then Reactional skin. In both Reactional skin and nerve TNF-alpha mRNA is more abundant than TNF-alpha protein; this may reflect the rapid turnover of TNF-alpha protein in an immunologically dynamic situation, such as is seen in Reversal Reaction. Our findings emphasize the importance of documenting both mRNA and protein production when assessing the role of cytokines in pathology. The leprosy Reversal Reaction may be regarded as a useful model of tissue immunopathology in which TNF-alpha is generated as part of the host response to infection, but also produces local tissue damage.
-
Tumour necrosis factor‐alpha (TNF‐α) synthesis is associated with the skin and peripheral nerve pathology of leprosy Reversal Reactions
Clinical and experimental immunology, 2008Co-Authors: S. Khanolkar-young, N B Rayment, Paul M Brickell, David R Katz, S Vinayakumar, M J Colston, Diana N. J. LockwoodAbstract:Leprosy may be complicated by episodes of increased cell-mediated immunity towards Mycobacterium leprae (Reversal Reactions) which result in severe local immunopathology in skin lesions and peripheral nerves. Using in situ hybridization and MoAb techniques we have demonstrated TNF-alpha mRNA and TNF-alpha protein in macrophages infiltrating leprosy skin and peripheral nerve. Levels of TNF-alpha mRNA are significantly increased in Reactional skin and nerve, particularly in borderline tuberculoid patients. TNF-alpha mRNA and TNF-alpha protein levels are higher in Reactional nerves then Reactional skin. In both Reactional skin and nerve TNF-alpha mRNA is more abundant than TNF-alpha protein; this may reflect the rapid turnover of TNF-alpha protein in an immunologically dynamic situation, such as is seen in Reversal Reaction. Our findings emphasize the importance of documenting both mRNA and protein production when assessing the role of cytokines in pathology. The leprosy Reversal Reaction may be regarded as a useful model of tissue immunopathology in which TNF-alpha is generated as part of the host response to infection, but also produces local tissue damage.
-
expression of cc and cxc chemokines and chemokine receptors in human leprosy skin lesions
Clinical and Experimental Immunology, 2003Co-Authors: A A Kirkaldy, A C Musonda, S Khanolkharyoung, Sujai Suneetha, Diana N. J. LockwoodAbstract:We have investigated the expression of chemokines and their receptors in leprosy skin lesions using immunohistochemistry. Skin biopsies from 25 leprosy patients across the leprosy spectrum, 11 patients undergoing type I Reversal Reactions and four normal donors were immunostained by ABC peroxidase method using antibodies against CC and CXC chemokines and their receptors. Using an in situ hybridization technique we have also studied the expression of monocyte chemoattractant protein 1 (MCP-1), RANTES and interleukin (IL)-8 chemokines mRNA in leprosy skin lesions. Chemokines and receptor expression was detected in all leprosy skin biopsies. Expression of CC chemokines MCP-1 (P < 0.01) and RANTES (P < 0.01) were elevated significantly in borderline tuberculoid leprosy in Reversal Reaction compared to non-Reactional borderline tuberculoid leprosy, but there was no difference in the expression of IL-8 chemokine. Surprisingly, there was no significant difference in the expression of CC (CCR2 and CCR5) and CXC (CXCR2) chemokine receptors across the leprosy spectrum. Similarly, there was no significant difference in the expression of mRNA for MCP-1, regulated upon activation normal T cell expressed and secreted (RANTES) and IL-8 chemokines. Here, the presence of a neutrophil chemoattractant IL-8 in leprosy lesions, which do not contain neutrophils, suggests strongly a role of IL-8 as a monocyte and lymphocyte recruiter in leprosy lesions. These results suggest that the chemokines and their receptors, which are known to chemoattract T lymphocytes and macrophages, are involved in assembling the cellular infiltrate found in lesions across the leprosy spectrum.
-
The detection of Mycobacterium leprae protein and carbohydrate antigens in skin and nerve from leprosy patients with type 1 (Reversal) Reactions.
The American journal of tropical medicine and hygiene, 2002Co-Authors: Diana N. J. Lockwood, M J Colston, Saroj Khanolkar-youngAbstract:Type 1 (Reversal) Reactions are the most common immunological complications of leprosy. These episodes of delayed hypersensitivity produce severe local immunopathology and ultimately nerve damage. To date, the Mycobacterium leprae antigens associated with type 1 Reactions have not been identified. Using monoclonal antibodies to defined protein and carbohydrate M. leprae epitopes (65, 35 and 28 kd and lipoarabinomannan [LAM]) in a two-step immunoperoxidase staining technique, M. leprae antigens were demonstrated in skin and nerve biopsies from patients in Reversal Reaction. Antigen presence and staining patterns were similar in skin and nerve lesions, implying that the pathological processes are similar in the two sites. Antigens were present both in macrophages and Schwann cells but also as a diffuse extracellular infiltrate associated with the inflammatory infiltrate. The 28-kd antigen was present most strongly and may be a potential candidate antigen for initiating type 1 Reactions. LAM also stained strongly and persisted after treatment. The possible roles of LAM and 65 kd in the cellular events of type 1 Reactions are discussed.
Euzenir Nunes Sarno - One of the best experts on this subject based on the ideXlab platform.
-
Neutrophils in Leprosy
Frontiers Media S.A., 2019Co-Authors: Veronica Schmitz, Isabella Forasteiro Tavares, Patricia Pignataro, Alice De Miranda Machado, Fabiana Dos Santos Pacheco, Jéssica Brandão Dos Santos, Camila Oliveira Da Silva, Euzenir Nunes SarnoAbstract:Leprosy is an infectious disease caused by the intracellular bacillus Mycobacterium leprae that mainly affects the skin and peripheral nerves. One of the most intriguing aspects of leprosy is the diversity of its clinical forms. Paucibacillary patients are characterized as having less than five skin lesions and rare bacilli while the lesions in multibacillary patients are disseminated with voluminous bacilli. The chronic course of leprosy is often interrupted by acute episodes of an inflammatory immunological response classified as either Reversal Reaction or erythema nodosum leprosum (ENL). Although ENL is considered a neutrophilic immune-complex mediated condition, little is known about the direct role of neutrophils in ENL and leprosy disease overall. Recent studies have shown a renewed interest in neutrophilic biology. One of the most interesting recent discoveries was that the neutrophilic population is not homogeneous. Neutrophilic polarization leads to divergent phenotypes (e.g., a pro- and antitumor profile) that are dynamic subpopulations with distinct phenotypical and functional abilities. Moreover, there is emerging evidence indicating that neutrophils expressing CD64 favor systemic inflammation during ENL. In the present review, neutrophilic involvement in leprosy is discussed with a particular focus on ENL and the potential of neutrophils as clinical biomarkers and therapeutic targets
-
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.
-
Corticosteroid therapy in borderline tuberculoid leprosy patients co-infected with HIV undergoing Reversal Reaction: a clinical study.
Leprosy review, 2016Co-Authors: Pedro José Secchin-de-andrade, Jose Augusto Da Costa Nery, Vinicius Martins Menezes, Mariana A. Hacker, Anna Maria Sales, Felipe Dalvi-garcia, Euzenir Nunes SarnoAbstract:Background Mycobacterium leprae and HIV cause infectious diseases of great concern for the public health care sector worldwide. Both are especially worrisome diseases when patients become co-infected and exhibit the expected clinical exuberance. The objective of this study was to evaluate episodes of Reversal Reaction (RR) and the effect of the use of corticosteroids on the treatment of borderline tuberculoid leprosy patients co-infected with the human immunodeficiency virus (HIV). Methods This is a retrospective cohort study in which the clinical manifestations of the patients and their responses to corticosteroid therapy were observed. Variables were analysed during and after multidrug therapy between the first and last days of prednisone, which occurred up to a maximum of 6 months after initiating corticosteroid therapy. Results A total of 22 HIV-positive and 28 HIV-negative cases were included. Loss of sensitivity and neural thickening were statistically significant while clinically ulcerated lesions were only observed in the co-infected group. Most patients were diagnosed with leprosy in the presence of RR and six patients manifested RR as an immune reconstitution inflammatory syndrome. On average, both groups received similar doses of corticosteroids (difference of 0·1 mg/kg/day).
-
type 1 Reaction in leprosy a model for a better understanding of tissue immunity under an immunopathological condition
Expert Review of Clinical Immunology, 2015Co-Authors: Priscila Ribeiro Andrade, Elizabeth P. Sampaio, Roberta Olmo Pinheiro, Jose Augusto Da Costa Nery, Mayara Garcia De Mattos Barbosa, Anna Maria Sales, Milton Ozório Moraes, Ximena Illarramendi, Marcia R Jardim, Euzenir Nunes SarnoAbstract:Type 1 Reaction (T1R) or Reversal Reaction is the leading cause of physical disabilities and deformities in leprosy. Leprosy patients, even after being considered cured and released from treatment, may suffer from Reactional episodes for long periods of time. Early diagnosis is a great challenge for effectively treating and managing T1R. There is an urgent need to identify the most significant biomarkers to prevent recurrent T1R and to differentiate late T1R from relapse. T1R continues to be treated with corticosteroids and complications due to iatrogenic treatment remain frequent. This review aims to provide a framework from which to approach the great challenges that still persist in T1R management and debate key issues in order to reduce the distance between basic research and the clinic.
-
role of cd8 t cells in triggering Reversal Reaction in hiv leprosy patients
Immunology, 2013Co-Authors: Ariane Leite De Oliveira, Roberta Olmo Pinheiro, Thais Porto Amadeu, Jose Augusto Da Costa Nery, Andressa Cristina De França Gomes, Vinicius Martins Menezes, Euzenir Nunes SarnoAbstract:It has been reported that the initiation of highly active anti-retroviral therapy (HAART) is associated with the development of Reversal Reaction (RR) in co-infected HIV/leprosy patients. Nevertheless, the impact of HIV and HAART on the cellular immune response to Mycobacterium leprae (ML) remains unknown. In the present study, we observed that ex vivo peripheral blood mononuclear cells (PBMCs) of both RR and RR/HIV patients presented increased percentages of activated CD4(+) T cells when compared with the healthy individuals (HC) group. The frequency of CD8(+) CD38(+) cells increased in the PBMCs of RR/HIV patients but not in RR patients when compared with the HC group. Both RR and RR/HIV skin lesion cells presented similar percentages of activated CD4(+) cells, but the numbers of activated CD8(+) cells were higher in RR/HIV in comparison to the RR group. The frequency of interferon-γ-producing cells was high in response to ML regardless of HIV co-infection. In ML-stimulated cells, there was an increase in central memory CD4(+) T-cell frequencies in the RR and RR/HIV groups, but an increase in central memory CD8(+) T-cell frequency was only observed in the RR/HIV group. ML increased granzyme B(+) effector memory CD8(+) T-cell frequencies in the RR/HIV PBMCs, but not in the HC and RR groups. Our data suggest that the increased expression of effector memory CD8(+) T cells, together with greater perforin/granzyme B production, could be an additional mechanism leading to the advent of RR in co-infected patients. Moreoever, this increased expression may explain the severity of RR occurring in these patients.
M J Colston - One of the best experts on this subject based on the ideXlab platform.
-
tumour necrosis factor alpha tnf α synthesis is associated with the skin and peripheral nerve pathology of leprosy Reversal Reactions
Clinical and Experimental Immunology, 2008Co-Authors: S Khanolkaryoung, N B Rayment, Paul M Brickell, David R Katz, S Vinayakumar, M J Colston, Diana N. J. LockwoodAbstract:SUMMARY Leprosy may be complicated by episodes of increased cell-mediated imtnunity tovk'ards Myco-bacterium leprae (Reversal Reactions) which result in severe local immunopathology in skin lesionsand peripheral nerves. Using in situ hybridization and MoAb techniques we have demonstratedTNF-a mRNA and TNF-o protein in macrophages infiltrating leprosy skin and peripheral nerve.Levels of TNF-Q mRNA are significantly increased in Reactional skin and nerve, particularly inborderline tubercuioid patients. TNF-o mRNA and TNF-Q protein levels are higher in Reactionalnerves then Reactional skin. In both Reactional skin and nerve TNF-a mRNA is more abundantthan TNF-a protein; this may reflect the rapid turnover of TNF-o protein in an immunologicallydynamic situation, such as is seen in Reversal Reaction. Our findings emphasize the importance ofdocumenting both mRNA and protein production when assessing the role of eytokines inpathology. The leprosy Reversal Reaction may be regarded as a useful model of tissue immuno-patbology in which TNF-a is generated as part of the host response to infection, but also produceslocal tissue damage.Keywords leprosy Reversal Reaction TNF In situ hybridization nerve damage
-
tumour necrosis factor alpha tnf α synthesis is associated with the skin and peripheral nerve pathology of leprosy Reversal Reactions
Clinical and Experimental Immunology, 2008Co-Authors: S Khanolkaryoung, N B Rayment, Paul M Brickell, David R Katz, S Vinayakumar, M J Colston, Diana N. J. LockwoodAbstract:Leprosy may be complicated by episodes of increased cell-mediated immunity towards Mycobacterium leprae (Reversal Reactions) which result in severe local immunopathology in skin lesions and peripheral nerves. Using in situ hybridization and MoAb techniques we have demonstrated TNF-alpha mRNA and TNF-alpha protein in macrophages infiltrating leprosy skin and peripheral nerve. Levels of TNF-alpha mRNA are significantly increased in Reactional skin and nerve, particularly in borderline tuberculoid patients. TNF-alpha mRNA and TNF-alpha protein levels are higher in Reactional nerves then Reactional skin. In both Reactional skin and nerve TNF-alpha mRNA is more abundant than TNF-alpha protein; this may reflect the rapid turnover of TNF-alpha protein in an immunologically dynamic situation, such as is seen in Reversal Reaction. Our findings emphasize the importance of documenting both mRNA and protein production when assessing the role of cytokines in pathology. The leprosy Reversal Reaction may be regarded as a useful model of tissue immunopathology in which TNF-alpha is generated as part of the host response to infection, but also produces local tissue damage.
-
Tumour necrosis factor‐alpha (TNF‐α) synthesis is associated with the skin and peripheral nerve pathology of leprosy Reversal Reactions
Clinical and experimental immunology, 2008Co-Authors: S. Khanolkar-young, N B Rayment, Paul M Brickell, David R Katz, S Vinayakumar, M J Colston, Diana N. J. LockwoodAbstract:Leprosy may be complicated by episodes of increased cell-mediated immunity towards Mycobacterium leprae (Reversal Reactions) which result in severe local immunopathology in skin lesions and peripheral nerves. Using in situ hybridization and MoAb techniques we have demonstrated TNF-alpha mRNA and TNF-alpha protein in macrophages infiltrating leprosy skin and peripheral nerve. Levels of TNF-alpha mRNA are significantly increased in Reactional skin and nerve, particularly in borderline tuberculoid patients. TNF-alpha mRNA and TNF-alpha protein levels are higher in Reactional nerves then Reactional skin. In both Reactional skin and nerve TNF-alpha mRNA is more abundant than TNF-alpha protein; this may reflect the rapid turnover of TNF-alpha protein in an immunologically dynamic situation, such as is seen in Reversal Reaction. Our findings emphasize the importance of documenting both mRNA and protein production when assessing the role of cytokines in pathology. The leprosy Reversal Reaction may be regarded as a useful model of tissue immunopathology in which TNF-alpha is generated as part of the host response to infection, but also produces local tissue damage.
-
The detection of Mycobacterium leprae protein and carbohydrate antigens in skin and nerve from leprosy patients with type 1 (Reversal) Reactions.
The American journal of tropical medicine and hygiene, 2002Co-Authors: Diana N. J. Lockwood, M J Colston, Saroj Khanolkar-youngAbstract:Type 1 (Reversal) Reactions are the most common immunological complications of leprosy. These episodes of delayed hypersensitivity produce severe local immunopathology and ultimately nerve damage. To date, the Mycobacterium leprae antigens associated with type 1 Reactions have not been identified. Using monoclonal antibodies to defined protein and carbohydrate M. leprae epitopes (65, 35 and 28 kd and lipoarabinomannan [LAM]) in a two-step immunoperoxidase staining technique, M. leprae antigens were demonstrated in skin and nerve biopsies from patients in Reversal Reaction. Antigen presence and staining patterns were similar in skin and nerve lesions, implying that the pathological processes are similar in the two sites. Antigens were present both in macrophages and Schwann cells but also as a diffuse extracellular infiltrate associated with the inflammatory infiltrate. The 28-kd antigen was present most strongly and may be a potential candidate antigen for initiating type 1 Reactions. LAM also stained strongly and persisted after treatment. The possible roles of LAM and 65 kd in the cellular events of type 1 Reactions are discussed.
-
Clinical features and outcome of Reversal (type 1) Reactions in Hyderabad, India.
International journal of leprosy and other mycobacterial diseases : official organ of the International Leprosy Association, 1993Co-Authors: Diana N. J. Lockwood, Solomon Vinayakumar, J. N. A. Stanley, K. P. W. J. Mcadam, M J ColstonAbstract:A retrospective survey of the notes on all patients attending Dhoolpet Leprosy Research Center, India, during 1985 was done to establish the frequency, timing, and clinical features of Reversal (type 1) Reactions; 494 case notes were examined and clinical evidence of a Reversal Reaction was found in 44 cases (10.9%). Reactions were most common in borderline patients, with 11.4% and 14.8% of borderline tuberculoid (BT) and borderline lepromatous (BL) patients developing Reactions, respectively. Presentation in Reaction was frequent with 47.5% of Reactional patients having signs of a Reversal Reaction at the time of their first visit to the Dhoolpet clinic; 50% of skin Reactions developing in patients on antileprosy treatment occur within the first month of treatment. Neurological Reactions occur later and over a longer time course. Late Reactions may occur up to 6 1/2 years after the start of treatment. Further Reactional episodes occurred in 31.8% of the patients, and may be repeated. Steroid treatment produced improvement of both skin lesions and neuritis, but improvement in clinical signs and symptoms occurred in only 50% of the neuritic episodes.
Jose Augusto Da Costa Nery - One of the best experts on this subject based on the ideXlab platform.
-
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.
-
Leprosum clots formed during serum harvesting of multibacillary patient.
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:A) Appearance of the leprosum clot during lepromatous patient serum harvesting, after blood coagulation and subsequent centrifugation. The vertical scale bar represents 2 cm and identifies the leprosum clot appearing on the top of normal erythrocyte-rich clot. B) The leprosum clot after PBS washing had a characteristic white-milky color. Scale bar represents 1 cm. C) Representation of a normal blood serum harvesting, after coagulation and subsequent centrifugation. D) Control clot aspect, formed from healthy donors’ plasma by the addition of calcium chloride; E) Leprosum clot distribution among 35 leprosy outpatients (11 females, 24 males; median age, 47.7 years; range, 10–76 years) discriminated by the clinical pole of the disease or presence/absence of Reactional episodes (F). G) Vascular abnormalities occurrence in patients who developed leprosum clot during serum harvesting (LC patients) or not (H). MB: multibacillary patients, PB: paucibacillary patients, ENL: erythema nodosum leprosum and T1R: Reversal Reaction.
-
Corticosteroid therapy in borderline tuberculoid leprosy patients co-infected with HIV undergoing Reversal Reaction: a clinical study.
Leprosy review, 2016Co-Authors: Pedro José Secchin-de-andrade, Jose Augusto Da Costa Nery, Vinicius Martins Menezes, Mariana A. Hacker, Anna Maria Sales, Felipe Dalvi-garcia, Euzenir Nunes SarnoAbstract:Background Mycobacterium leprae and HIV cause infectious diseases of great concern for the public health care sector worldwide. Both are especially worrisome diseases when patients become co-infected and exhibit the expected clinical exuberance. The objective of this study was to evaluate episodes of Reversal Reaction (RR) and the effect of the use of corticosteroids on the treatment of borderline tuberculoid leprosy patients co-infected with the human immunodeficiency virus (HIV). Methods This is a retrospective cohort study in which the clinical manifestations of the patients and their responses to corticosteroid therapy were observed. Variables were analysed during and after multidrug therapy between the first and last days of prednisone, which occurred up to a maximum of 6 months after initiating corticosteroid therapy. Results A total of 22 HIV-positive and 28 HIV-negative cases were included. Loss of sensitivity and neural thickening were statistically significant while clinically ulcerated lesions were only observed in the co-infected group. Most patients were diagnosed with leprosy in the presence of RR and six patients manifested RR as an immune reconstitution inflammatory syndrome. On average, both groups received similar doses of corticosteroids (difference of 0·1 mg/kg/day).
-
type 1 Reaction in leprosy a model for a better understanding of tissue immunity under an immunopathological condition
Expert Review of Clinical Immunology, 2015Co-Authors: Priscila Ribeiro Andrade, Elizabeth P. Sampaio, Roberta Olmo Pinheiro, Jose Augusto Da Costa Nery, Mayara Garcia De Mattos Barbosa, Anna Maria Sales, Milton Ozório Moraes, Ximena Illarramendi, Marcia R Jardim, Euzenir Nunes SarnoAbstract:Type 1 Reaction (T1R) or Reversal Reaction is the leading cause of physical disabilities and deformities in leprosy. Leprosy patients, even after being considered cured and released from treatment, may suffer from Reactional episodes for long periods of time. Early diagnosis is a great challenge for effectively treating and managing T1R. There is an urgent need to identify the most significant biomarkers to prevent recurrent T1R and to differentiate late T1R from relapse. T1R continues to be treated with corticosteroids and complications due to iatrogenic treatment remain frequent. This review aims to provide a framework from which to approach the great challenges that still persist in T1R management and debate key issues in order to reduce the distance between basic research and the clinic.
-
role of cd8 t cells in triggering Reversal Reaction in hiv leprosy patients
Immunology, 2013Co-Authors: Ariane Leite De Oliveira, Roberta Olmo Pinheiro, Thais Porto Amadeu, Jose Augusto Da Costa Nery, Andressa Cristina De França Gomes, Vinicius Martins Menezes, Euzenir Nunes SarnoAbstract:It has been reported that the initiation of highly active anti-retroviral therapy (HAART) is associated with the development of Reversal Reaction (RR) in co-infected HIV/leprosy patients. Nevertheless, the impact of HIV and HAART on the cellular immune response to Mycobacterium leprae (ML) remains unknown. In the present study, we observed that ex vivo peripheral blood mononuclear cells (PBMCs) of both RR and RR/HIV patients presented increased percentages of activated CD4(+) T cells when compared with the healthy individuals (HC) group. The frequency of CD8(+) CD38(+) cells increased in the PBMCs of RR/HIV patients but not in RR patients when compared with the HC group. Both RR and RR/HIV skin lesion cells presented similar percentages of activated CD4(+) cells, but the numbers of activated CD8(+) cells were higher in RR/HIV in comparison to the RR group. The frequency of interferon-γ-producing cells was high in response to ML regardless of HIV co-infection. In ML-stimulated cells, there was an increase in central memory CD4(+) T-cell frequencies in the RR and RR/HIV groups, but an increase in central memory CD8(+) T-cell frequency was only observed in the RR/HIV group. ML increased granzyme B(+) effector memory CD8(+) T-cell frequencies in the RR/HIV PBMCs, but not in the HC and RR groups. Our data suggest that the increased expression of effector memory CD8(+) T cells, together with greater perforin/granzyme B production, could be an additional mechanism leading to the advent of RR in co-infected patients. Moreoever, this increased expression may explain the severity of RR occurring in these patients.
N B Rayment - One of the best experts on this subject based on the ideXlab platform.
-
tumour necrosis factor alpha tnf α synthesis is associated with the skin and peripheral nerve pathology of leprosy Reversal Reactions
Clinical and Experimental Immunology, 2008Co-Authors: S Khanolkaryoung, N B Rayment, Paul M Brickell, David R Katz, S Vinayakumar, M J Colston, Diana N. J. LockwoodAbstract:SUMMARY Leprosy may be complicated by episodes of increased cell-mediated imtnunity tovk'ards Myco-bacterium leprae (Reversal Reactions) which result in severe local immunopathology in skin lesionsand peripheral nerves. Using in situ hybridization and MoAb techniques we have demonstratedTNF-a mRNA and TNF-o protein in macrophages infiltrating leprosy skin and peripheral nerve.Levels of TNF-Q mRNA are significantly increased in Reactional skin and nerve, particularly inborderline tubercuioid patients. TNF-o mRNA and TNF-Q protein levels are higher in Reactionalnerves then Reactional skin. In both Reactional skin and nerve TNF-a mRNA is more abundantthan TNF-a protein; this may reflect the rapid turnover of TNF-o protein in an immunologicallydynamic situation, such as is seen in Reversal Reaction. Our findings emphasize the importance ofdocumenting both mRNA and protein production when assessing the role of eytokines inpathology. The leprosy Reversal Reaction may be regarded as a useful model of tissue immuno-patbology in which TNF-a is generated as part of the host response to infection, but also produceslocal tissue damage.Keywords leprosy Reversal Reaction TNF In situ hybridization nerve damage
-
tumour necrosis factor alpha tnf α synthesis is associated with the skin and peripheral nerve pathology of leprosy Reversal Reactions
Clinical and Experimental Immunology, 2008Co-Authors: S Khanolkaryoung, N B Rayment, Paul M Brickell, David R Katz, S Vinayakumar, M J Colston, Diana N. J. LockwoodAbstract:Leprosy may be complicated by episodes of increased cell-mediated immunity towards Mycobacterium leprae (Reversal Reactions) which result in severe local immunopathology in skin lesions and peripheral nerves. Using in situ hybridization and MoAb techniques we have demonstrated TNF-alpha mRNA and TNF-alpha protein in macrophages infiltrating leprosy skin and peripheral nerve. Levels of TNF-alpha mRNA are significantly increased in Reactional skin and nerve, particularly in borderline tuberculoid patients. TNF-alpha mRNA and TNF-alpha protein levels are higher in Reactional nerves then Reactional skin. In both Reactional skin and nerve TNF-alpha mRNA is more abundant than TNF-alpha protein; this may reflect the rapid turnover of TNF-alpha protein in an immunologically dynamic situation, such as is seen in Reversal Reaction. Our findings emphasize the importance of documenting both mRNA and protein production when assessing the role of cytokines in pathology. The leprosy Reversal Reaction may be regarded as a useful model of tissue immunopathology in which TNF-alpha is generated as part of the host response to infection, but also produces local tissue damage.
-
Tumour necrosis factor‐alpha (TNF‐α) synthesis is associated with the skin and peripheral nerve pathology of leprosy Reversal Reactions
Clinical and experimental immunology, 2008Co-Authors: S. Khanolkar-young, N B Rayment, Paul M Brickell, David R Katz, S Vinayakumar, M J Colston, Diana N. J. LockwoodAbstract:Leprosy may be complicated by episodes of increased cell-mediated immunity towards Mycobacterium leprae (Reversal Reactions) which result in severe local immunopathology in skin lesions and peripheral nerves. Using in situ hybridization and MoAb techniques we have demonstrated TNF-alpha mRNA and TNF-alpha protein in macrophages infiltrating leprosy skin and peripheral nerve. Levels of TNF-alpha mRNA are significantly increased in Reactional skin and nerve, particularly in borderline tuberculoid patients. TNF-alpha mRNA and TNF-alpha protein levels are higher in Reactional nerves then Reactional skin. In both Reactional skin and nerve TNF-alpha mRNA is more abundant than TNF-alpha protein; this may reflect the rapid turnover of TNF-alpha protein in an immunologically dynamic situation, such as is seen in Reversal Reaction. Our findings emphasize the importance of documenting both mRNA and protein production when assessing the role of cytokines in pathology. The leprosy Reversal Reaction may be regarded as a useful model of tissue immunopathology in which TNF-alpha is generated as part of the host response to infection, but also produces local tissue damage.