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1.
Adv Rheumatol ; 59(1): 52, 2019 11 28.
Artículo en Inglés | MEDLINE | ID: mdl-31779703

RESUMEN

INTRODUCTION: Antiphospholipid antibodies (aPL) are described in individuals with leprosy without the clinical features of antiphospholipid antibody syndrome (APS), a condition involving thromboembolic phenomena. We have described the persistence of these antibodies for over 5 years in patients with leprosy after specific treatment. OBJECTIVES: To determine whether epidemiological, clinical and immunological factors played a role in the long-term persistence of aPL antibodies in leprosy patients after multidrug therapy (MDT) had finished. METHODS: The study sample consisted of 38 patients with a diagnosis of leprosy being followed up at the Dermatology and Venereology Outpatient Department at the Alfredo da Matta Foundation (FUAM) in Manaus, AM. ELISA was used to detect anticardiolipin (aCL) and anti-ß2 glycoprotein I (anti-ß2GPI) antibodies. Patients were reassessed on average of 5 years after specific treatment for the disease (MDT) had been completed. RESULTS: Persistence of aPL antibodies among the 38 leprosy patients was 84% (32/38), and all had the IgM isotype. Mean age was 48.1 ± 15.9 years, and 23 (72.0%) were male. The lepromatous form (LL) of leprosy was the most common (n = 16, 50%). Reactional episodes were observed in three patients (9.4%). Eighteen (47.37%) were still taking medication (prednisone and/or thalidomide). Mean IgM levels were 64 U/mL for aCL and 62 U/mL for anti-ß2GPI. In the multivariate binary logistic regression the following variables showed a significant association: age (p = 0.045, OR = 0.91 and CI 95% 0.82-0.98), LL clinical presention (p = 0.034; OR = 0.02 and CI 95% = 0.0-0.76) and bacterial index (p = 0.044; OR = 2.74 and CI 95% = 1.03-7.33). We did not find association between prednisone or thalidomide doses and positivity for aPL (p = 0.504 and p = 0.670, respectively). No differences in the variables vascular thrombosis, pregnancy morbidity, diabetes, smoking and alcoholism were found between aPL-positive and aPL-negative patients. CONCLUSION: Persistence of positivity for aPL antibodies was influenced by age, clinical presentation and bacterial index. However, further studies are needed to elucidate the reason for this persistence, the role played by aPL antibodies in the disease and the B cell lineages responsible for generation of these antibodies.


Asunto(s)
Anticuerpos Antifosfolípidos/sangre , Lepra/inmunología , beta 2 Glicoproteína I/inmunología , Adulto , Anticuerpos Anticardiolipina/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Leprostáticos/uso terapéutico , Lepra/sangre , Lepra/tratamiento farmacológico , Lepra Multibacilar/sangre , Lepra Multibacilar/tratamiento farmacológico , Lepra Multibacilar/inmunología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Talidomida/uso terapéutico
2.
Skinmed ; 17(4): 261-265, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31627788

RESUMEN

In Type II lepromatous reaction, there is exacerbation of humoral immunity, classified as Gell & Coombs Type III hypersensitivity reaction. It is more common in lepromatous borderline (LB) and lepromatous lepromatous (LL) patients. Our objective was to study the clinical and laboratorial expressions of lepromatous Type II reactions, establishing concordances between them, and for this the medical records of leprosy patients observed at the Clementino Fraga Filho University Hospital of the Federal University of Rio de Janeiro (HUCFF/UFRJ) were reviewed. There were a total of 358 leprosy cases over a period of 12 years. Demographic, clinical, and laboratory data of 133 patients with Type II reaction were collected. Among the 133 patients, 19 were classified as borderline borderline (BB), 15 (11.3%) as LB, and 97 (72.9%) as LL. Mitsuda intradermal reaction was negative in all the 49 patients who underwent this test. Histopathologic study confirmed the diagnosis. Lepromatous patients (LP) presented positive bacilloscopy more frequently (73.91% of 68 patients) than borderline patients (BP) (26.9% of 24 patients). Among BP, 44% presented erythema nodosum leprosum (ENL), which was seen in 71% of LP. Erythema multiforme (EM) occurred in 32% of BP and 13% of LP. Lucio phenomenon (LPh) was observed in 8 of 34 BP (23.6%), and 15 of 97 LP (15.4%). The understanding of the laboratorial and clinical presentations of reactional episodes are relevant to the development of preventive and therapeutic strategies, in order to avoid potential complications and comorbidities that cause disability, paralysis, deformities, and stigma of leprosy.


Asunto(s)
Lepra Multibacilar/inmunología , Adolescente , Adulto , Anciano , Brasil/epidemiología , Niño , Femenino , Humanos , Lepra Lepromatosa/sangre , Lepra Lepromatosa/clasificación , Lepra Lepromatosa/epidemiología , Lepra Lepromatosa/inmunología , Lepra Multibacilar/sangre , Lepra Multibacilar/clasificación , Lepra Multibacilar/epidemiología , Masculino , Persona de Mediana Edad , Adulto Joven
3.
Trials ; 19(1): 244, 2018 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-29685164

RESUMEN

BACKGROUND: The annual new-case detection rate for leprosy, while generally stable over the last decade, shows that transmission rates have remained stagnant despite the successful worldwide administration of multidrug therapy since the 1980s. As such, novel control strategies are urgently needed. Focusing on managing leprosy patient contacts, the most susceptible to contracting the disease, has been seen as a potential strategy in limiting the spread of leprosy as shown by a number of recent epidemiological studies. Immunoprophylaxis with Bacillus Calmette-Guérin (BCG) has been seen as an effective preventive measure due to its ability to stimulate the development of cellular immunity which is essential in controlling the disease, especially in its multibacillary (MB) forms. The association of immunoprophylaxis with chemoprophylaxis in a single dose of rifampicin has been shown to be a promising preventive strategy, although a variety of studies have found instances of early case detection just a few months after BCG vaccination. METHODS/DESIGN: The present study is a phase IV chemoprophylactic clinical trial consisting of administration of a single dose of rifampicin in MB leprosy patient contacts under care at the Souza Araújo Outpatient Clinic/FIOCRUZ as part of a randomized (2:1), double-blind, placebo-controlled study. It is comprised of two groups: 1) rifampicin + BCG; and 2) placebo + BCG. DISCUSSION: The aim is to evaluate whether the use of chemoprophylaxis with a single dose of rifampicin in MB leprosy patient contacts prior to the BCG vaccine would be able to prevent the onset of leprosy in those cases that may occur just a few months after vaccination. Contact subclinical infections (polymerase chain reaction) and the immunological parameters (anti-PGL-1, anti-LID-1, and IFN-γ) will be evaluated and the results will be compared after 12 months of follow-up. TRIAL REGISTRATION: The Brazilian Registry of Clinical Trials (ReBEC), RBR-69QK5P . Retrospectively registered on 1 June 2017.


Asunto(s)
Vacuna BCG/administración & dosificación , Trazado de Contacto , Leprostáticos/administración & dosificación , Lepra Multibacilar/prevención & control , Rifampin/administración & dosificación , Adolescente , Adulto , Anciano , Vacuna BCG/efectos adversos , Brasil , Niño , Preescolar , Ensayos Clínicos Fase IV como Asunto , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Lactante , Leprostáticos/efectos adversos , Lepra Multibacilar/inmunología , Lepra Multibacilar/microbiología , Lepra Multibacilar/transmisión , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Rifampin/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Vacunación , Adulto Joven
4.
Mem Inst Oswaldo Cruz ; 113(5): e170467, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29513821

RESUMEN

BACKGROUND Leprosy remains a health problem in many countries, with difficulties in diagnosis resulting in delayed treatment and more severe disabilities. Antibodies against several Mycobacterium leprae antigens have, however, shown value as diagnostic and/or prognostic markers. OBJECTIVES The objective of this study was to evaluate serum immunoglobulin (Ig) IgM and IgG subclass reactivity against three M. leprae specific antigens: NDO-HSA, a conjugate formed by natural octyl disaccharide bound to human serum albumin; LID-1, the fusion protein product of the ml0405 and ml2331 genes; and NDO-LID, a combination of LID-1 and NDO. METHODS Sera from healthy controls, paucibacillary (PB) and multibacillary (MB) leprosy patients, and their respective household contacts, were evaluated for the presence of antigen-specific IgM, IgG, and IgG subclass antibodies by enzyme-linked immunosorbent assay (ELISA). The sensitivity and specificity of each ELISA were evaluated by receiver operating characteristic (ROC) curve analysis. FINDINGS Our data confirm that serum IgM antibodies against NDO-HSA and IgG antibodies against LID-1, as well as IgG/M antibodies against NDO-LID, are markedly increased in MB patients. For the first time, our data reveal a selective increase in IgG1 and IgG3 antibodies against LID-1 and NDO-LID in MB patients, demonstrating that these antibody isotypes are suitable for differentiation between MB and PB patients. ROC curve analysis indicates an improved capacity for diagnosing MB leprosy patients using the detection of IgG antibodies, particularly the IgG1 isotype, specific to LID-1 and NDO-LID over the performance levels attained with NDO-HSA. CONCLUSIONS Our findings indicate that serological tests based on the detection of antigen-specific IgG1 antibodies are a useful tool to differentiate MB from PB patients, and indicate the enhanced performance of the LID-1 and NDO-LID antigens in the serodiagnosis of leprosy.


Asunto(s)
Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Lepra Multibacilar/diagnóstico , Lepra Paucibacilar/diagnóstico , Estudios de Casos y Controles , Trazado de Contacto , Ensayo de Inmunoadsorción Enzimática , Humanos , Lepra Multibacilar/inmunología , Lepra Paucibacilar/inmunología , Mycobacterium leprae/inmunología , Curva ROC , Sensibilidad y Especificidad
5.
Rev Soc Bras Med Trop ; 51(1): 99-104, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29513853

RESUMEN

INTRODUCTION: Corticosteroids and/or thalidomides have been associated with thromboembolism events (TBE) in multibacillary (MB) leprosy. This report aimed to determine genetic and laboratory profiles associated with leprosy and TBE. METHODS: Antiphospholipid antibodies (aPL), coagulation-related exams, prothrombin and Leiden's factor V mutations, and ß2-glycoprotein-I (ß2GPI) Val247Leu polymorphism were assessed. RESULTS: Six out of seven patients with leprosy were treated with prednisone and/or thalidomide during TBE and presented at least one positive aPL. All patients presented ß2GPI polymorphism, and one showed prothrombin mutation. CONCLUSIONS: Corticosteroid or thalidomide adverse effects and aPL and ß2GPI polymorphisms may cause TBE in patients with MB leprosy.


Asunto(s)
Corticoesteroides/administración & dosificación , Síndrome Antifosfolípido , Lepra Multibacilar/inmunología , Talidomida/administración & dosificación , Corticoesteroides/efectos adversos , Adulto , Anciano , Anticuerpos Antifosfolípidos/sangre , Anticuerpos Antifosfolípidos/efectos de los fármacos , Anticuerpos Antifosfolípidos/genética , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/tratamiento farmacológico , Síndrome Antifosfolípido/genética , Ensayo de Inmunoadsorción Enzimática , Factor V/análisis , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Lepra Multibacilar/tratamiento farmacológico , Lepra Multibacilar/genética , Masculino , Persona de Mediana Edad , Mutación , Polimorfismo Genético , Protrombina/análisis , Talidomida/efectos adversos , Tromboembolia Venosa/tratamiento farmacológico , beta 2 Glicoproteína I/sangre
6.
Rev. Soc. Bras. Med. Trop ; 51(1): 99-104, Jan.-Feb. 2018. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1041441

RESUMEN

Abstract INTRODUCTION Corticosteroids and/or thalidomides have been associated with thromboembolism events (TBE) in multibacillary (MB) leprosy. This report aimed to determine genetic and laboratory profiles associated with leprosy and TBE. METHODS Antiphospholipid antibodies (aPL), coagulation-related exams, prothrombin and Leiden's factor V mutations, and ß2-glycoprotein-I (ß2GPI) Val247Leu polymorphism were assessed. RESULTS Six out of seven patients with leprosy were treated with prednisone and/or thalidomide during TBE and presented at least one positive aPL. All patients presented ß2GPI polymorphism, and one showed prothrombin mutation. CONCLUSIONS Corticosteroid or thalidomide adverse effects and aPL and ß2GPI polymorphisms may cause TBE in patients with MB leprosy.


Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Anciano , Talidomida/administración & dosificación , Síndrome Antifosfolípido/genética , Síndrome Antifosfolípido/tratamiento farmacológico , Síndrome Antifosfolípido/sangre , Corticoesteroides/administración & dosificación , Lepra Multibacilar/inmunología , Polimorfismo Genético , Talidomida/efectos adversos , Factor V/análisis , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Protrombina/análisis , Ensayo de Inmunoadsorción Enzimática , Anticuerpos Antifosfolípidos/efectos de los fármacos , Anticuerpos Antifosfolípidos/genética , Anticuerpos Antifosfolípidos/sangre , Corticoesteroides/efectos adversos , beta 2 Glicoproteína I/sangre , Tromboembolia Venosa/tratamiento farmacológico , Lepra Multibacilar/genética , Lepra Multibacilar/tratamiento farmacológico , Persona de Mediana Edad , Mutación
7.
Front Immunol ; 9: 2920, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30631322

RESUMEN

Leprosy is a chronic disease caused by M. leprae infection that can cause severe neurological complications and physical disabilities. A leprosy-specific vaccine would be an important component within control programs but is still lacking. Given that multifunctional CD4 T cells [i.e., those capable of simultaneously secreting combinations of interferon (IFN)-γ, interleukin (IL)-2, and tumor necrosis factor (TNF)] have now been implicated in the protective response to several infections, we tested the hypothesis if a recombinant M. leprae antigen-specific multifunctional T cells differed between leprosy patients and their healthy contacts. We used whole blood assays and peripheral blood mononuclear cells to characterize the antigen-specific T cell responses of 39 paucibacillary (PB) and 17 multibacillary (MB) leprosy patients and 31 healthy household contacts (HHC). Cells were incubated with either crude mycobacterial extracts (M. leprae cell sonicate-MLCS) and purified protein derivative (PPD) or recombinant ML2028 protein, the homolog of M. tuberculosis Ag85B. Multiplex assay revealed antigen-specific production of IFN-γ and IL-2 from cells of HHC and PB, confirming a Th1 bias within these individuals. Multiparameter flow cytometry then revealed that the population of multifunctional ML2028-specific T cells observed in HHC was larger than that observed in PB patients. Taken together, our data suggest that these multifunctional antigen-specific T cells provide a more effective response against M. leprae infection that prevents the development of leprosy. These data further our understanding of M. leprae infection/leprosy and are instructive for vaccine development.


Asunto(s)
Antígenos Bacterianos/inmunología , Linfocitos T CD4-Positivos/inmunología , Lepra Multibacilar/inmunología , Lepra Paucibacilar/inmunología , Mycobacterium leprae/inmunología , Vacunas/inmunología , Adulto , Anciano , Antígenos Bacterianos/genética , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/microbiología , Femenino , Humanos , Interferón gamma/inmunología , Interferón gamma/metabolismo , Interleucina-2/inmunología , Interleucina-2/metabolismo , Lepra Multibacilar/microbiología , Lepra Multibacilar/prevención & control , Lepra Paucibacilar/microbiología , Lepra Paucibacilar/prevención & control , Masculino , Persona de Mediana Edad , Mycobacterium leprae/fisiología , Proteínas Recombinantes/inmunología , Células TH1/inmunología , Células TH1/metabolismo , Vacunas/uso terapéutico , Adulto Joven
8.
Rev Soc Bras Med Trop ; 50(2): 208-215, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28562757

RESUMEN

INTRODUCTION: : Currently, there are no laboratory tests or sensitive and specific molecular markers for the early diagnosis of leprosy. The aim of this study was to analyze the clinical characteristics of patients with leprosy and investigate their immunological profile, comparing this with the type of lesion and the presence or absence of a Bacillus Calmette-Guérin (BCG) vaccination scar. METHODS:: Statistical analyzes were performed by employing comparative tests (Pearson´s chi-square) to evaluate the variables in different clinical forms, considering significance at the 5% level. RESULTS: : The study identified a predominance of lepromatous leprosy (26.9%) in patients aged between 34-53 years. Caucasians predominantly had borderline tuberculoid (BT) clinical forms (42%); a predominance of males with borderline lepromatous (19%) and lepromatous leprosy (26.9%) forms was observed; and the presence of BCG vaccination scars (27.5%) and lower limb nerves were more affected (38%) predominantly in the BT clinical form. Significant differences were identified, which included hypochromic lesions predominantly in the BT clinical form (24%); diffuse-type lesions predominantly in the tuberculoid (TT) clinical form (28%); ill-defined lesion border dominance in lepromatous leprosy (LL) clinical forms (30%); an irregular lesion limit predominantly in LL clinical forms (32%); and a predominant Th1 immune response in the BT clinical form (41.7%). CONCLUSIONS: : The evaluation of the immunological profile in leprosy patients may contribute to the more detailed diagnosis and possibly better characterization of the prognosis for these individuals.


Asunto(s)
Lepra Multibacilar/diagnóstico , Lepra Multibacilar/inmunología , Lepra Paucibacilar/diagnóstico , Lepra Paucibacilar/inmunología , Células TH1/inmunología , Células Th2/inmunología , Adolescente , Adulto , Biopsia , Estudios Transversales , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Lepra Multibacilar/clasificación , Lepra Paucibacilar/clasificación , Masculino , Persona de Mediana Edad , Células TH1/metabolismo , Adulto Joven
9.
PLoS Negl Trop Dis ; 11(5): e0005560, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28467415

RESUMEN

Household contacts of multibacillary leprosy patients (HCMB) constitute the group of individuals at the highest risk of developing leprosy. Early diagnosis and treatment of their index cases combined with Bacille Calmette-Guerin (BCG) immunization remain important strategies adopted in Brazil to prevent HCMB from evolving into active disease. In the present study, we assessed the impact of these measures on the immune response to Mycobacterium leprae in HCMB. Peripheral blood mononuclear cells (PBMC) from HCMB (n = 16) were obtained at the beginning of leprosy index case treatment (T0). At this time point, contacts were vaccinated (n = 13) or not (n = 3) in accordance with their infancy history of BCG vaccination and PBMCs were recollected at least 6 months later (T1). As expected, a significant increase in memory CD4 and CD8 T cell frequencies responsive to M. leprae whole-cell sonicate was observed in most contacts. Of note, higher frequencies of CD4+ T cells that recognize M. leprae specific epitopes were also detected. Moreover, increased production of the inflammatory mediators IL1-ß, IL-6, IL-17, TNF, IFN-γ, MIP1-ß, and MCP-1 was found at T1. Interestingly, the increment in these parameters was observed even in those contacts that were not BCG vaccinated at T0. This result reinforces the hypothesis that the continuous exposure of HCMB to live M. leprae down regulates the specific cellular immune response against the pathogen. Moreover, our data suggest that BCG vaccination of HCMB induces activation of T cell clones, likely through "trained immunity", that recognize M. leprae specific antigens not shared with BCG as an additional protective mechanism besides the expected boost in cell-mediated immunity by BCG homologues of M. leprae antigens.


Asunto(s)
Antígenos Bacterianos/inmunología , Vacuna BCG/uso terapéutico , Linfocitos T CD4-Positivos/inmunología , Inmunidad Celular , Lepra Multibacilar/inmunología , Adulto , Anticuerpos Antibacterianos/sangre , Brasil , Linfocitos T CD8-positivos/inmunología , Citocinas/metabolismo , Epítopos de Linfocito T/inmunología , Composición Familiar , Femenino , Humanos , Inmunoglobulina M/sangre , Lepra Multibacilar/prevención & control , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Mycobacterium leprae , Estudios Prospectivos , Adulto Joven
10.
Scand J Immunol ; 86(1): 40-49, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28426172

RESUMEN

It is well established that helper T cell responses influence resistance or susceptibility to Mycobacterium leprae infection, but the role of more recently described helper T cell subsets in determining severity is less clear. To investigate the involvement of Th17 cells in the pathogenesis of leprosy, we determined the immune profile with variant presentations of leprosy. Firstly, IL-17A, IFN-γ and IL-10 were evaluated in conjunction with CD4+ T cell staining by confocal microscopy of lesion biopsies from tuberculoid (TT) and lepromatous leprosy (LL) patients. Secondly, inflammatory cytokines were measured by multiplex assay of serum samples from Multibacillary (MB, n = 28) and Paucibacillary (PB, n = 23) patients and household contacts (HHC, n = 23). Patients with leprosy were also evaluated for leprosy reaction occurrence: LR+ (n = 8) and LR- (n = 20). Finally, peripheral blood mononuclear cells were analysed by flow cytometry used to determine the phenotype of cytokine-producing cells. Lesions from TT patients were found to have more CD4+ IL-17A+ cells than those from LL patients. Higher concentrations of IL-17A and IL-1ß were observed in serum from PB than MB patients. The highest serum IFN-γ concentrations were, however, detected in sera from MB patients that developed leprosy reactions (MB LR+ ). Together, these results indicate that Th1 cells were associated with both the PB presentation and also with leprosy reactions. In contrast, Th17 cells were associated with an effective inflammatory response that is present in the PB forms but were not predictive of leprosy reactions in MB patients.


Asunto(s)
Mediadores de Inflamación/inmunología , Lepra Paucibacilar/inmunología , Lepra/inmunología , Mycobacterium leprae/inmunología , Células TH1/inmunología , Células Th17/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Niño , Trazado de Contacto , Femenino , Citometría de Flujo , Humanos , Mediadores de Inflamación/sangre , Mediadores de Inflamación/metabolismo , Interferón gamma/sangre , Interferón gamma/inmunología , Interferón gamma/metabolismo , Interleucina-10/sangre , Interleucina-10/inmunología , Interleucina-10/metabolismo , Interleucina-17/sangre , Interleucina-17/inmunología , Interleucina-17/metabolismo , Interleucina-1beta/sangre , Interleucina-1beta/inmunología , Interleucina-1beta/metabolismo , Lepra/sangre , Lepra/microbiología , Lepra Multibacilar/sangre , Lepra Multibacilar/inmunología , Lepra Multibacilar/microbiología , Lepra Paucibacilar/sangre , Lepra Paucibacilar/microbiología , Masculino , Microscopía Confocal , Persona de Mediana Edad , Mycobacterium leprae/fisiología , Células TH1/metabolismo , Células Th17/metabolismo , Adulto Joven
11.
Rev. Soc. Bras. Med. Trop ; 50(2): 208-215, Mar.-Apr. 2017. tab, graf
Artículo en Inglés | LILACS | ID: biblio-842843

RESUMEN

Abstract INTRODUCTION: Currently, there are no laboratory tests or sensitive and specific molecular markers for the early diagnosis of leprosy. The aim of this study was to analyze the clinical characteristics of patients with leprosy and investigate their immunological profile, comparing this with the type of lesion and the presence or absence of a Bacillus Calmette-Guérin (BCG) vaccination scar. METHODS: Statistical analyzes were performed by employing comparative tests (Pearson´s chi-square) to evaluate the variables in different clinical forms, considering significance at the 5% level. RESULTS: The study identified a predominance of lepromatous leprosy (26.9%) in patients aged between 34-53 years. Caucasians predominantly had borderline tuberculoid (BT) clinical forms (42%); a predominance of males with borderline lepromatous (19%) and lepromatous leprosy (26.9%) forms was observed; and the presence of BCG vaccination scars (27.5%) and lower limb nerves were more affected (38%) predominantly in the BT clinical form. Significant differences were identified, which included hypochromic lesions predominantly in the BT clinical form (24%); diffuse-type lesions predominantly in the tuberculoid (TT) clinical form (28%); ill-defined lesion border dominance in lepromatous leprosy (LL) clinical forms (30%); an irregular lesion limit predominantly in LL clinical forms (32%); and a predominant Th1 immune response in the BT clinical form (41.7%). CONCLUSIONS: The evaluation of the immunological profile in leprosy patients may contribute to the more detailed diagnosis and possibly better characterization of the prognosis for these individuals.


Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Adulto Joven , Células Th2/inmunología , Células TH1/inmunología , Lepra Multibacilar/diagnóstico , Lepra Multibacilar/inmunología , Lepra Paucibacilar/diagnóstico , Lepra Paucibacilar/inmunología , Biopsia , Estudios Transversales , Técnica del Anticuerpo Fluorescente , Células TH1/metabolismo , Lepra Multibacilar/clasificación , Lepra Paucibacilar/clasificación , Persona de Mediana Edad
12.
Exp Dermatol ; 26(10): 946-948, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28109171

RESUMEN

This study, for the first time, reveals the role of M. leprae-specific CD4+ TCRγδ+ FoxP3+ cells in the progression and pathogenesis of leprosy. Co-culture with CD4+ CD25- cells suggested the immunosuppressive nature of CD4+ TCRγδ+ cells in dose-dependent manner. Isolation of CD4+ TCRγδ+ cells from leprosy patients and then culture in presence of M. leprae cell wall antigens (MLCwA) along with TGF ß, IPP and IL-2 suggested that these cells are M. leprae specific. TGF-ß-mediated SMAD3 signalling was turned out to be major factor towards the expression of FoxP3 in these cells. SMAD3 silencing during induction of these cells barely showed the induction of FoxP3. High density of SMAD3 binding at TGFßRII in CD4+ TCRγδ+ FoxP3+ furthermore suggested the TGF-ß-directed SMAD3 signalling in these cells. Taken together the above data, we can conclude that CD4+ TCRγδ+ FoxP3+ cells possess the potential to track the severity of the disease in leprosy patients.


Asunto(s)
Linfocitos T CD4-Positivos/metabolismo , Tolerancia Inmunológica , Lepra Multibacilar/inmunología , Lepra Paucibacilar/inmunología , Proteína smad3/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Progresión de la Enfermedad , Factores de Transcripción Forkhead/metabolismo , Humanos , Interferón gamma/sangre , Interleucina-17/sangre , Lepra Multibacilar/sangre , Lepra Paucibacilar/sangre , Mycobacterium leprae/inmunología , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Índice de Severidad de la Enfermedad , Transducción de Señal
13.
Appl Microbiol Biotechnol ; 100(7): 3267-75, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26820649

RESUMEN

Despite control efforts, leprosy persists as a significant health concern in many regions. Diagnosis is achieved by a combination of clinical, histopathological, and bacteriological examinations, each of which presents a barrier to expeditious diagnosis, particularly by non-experts. Immunological investigations in research laboratories have clearly indicated that antibody detection tests could aid the diagnosis of leprosy. In this study, we detected circulating antibodies with two rapid diagnostic tests (RDT) involving immunochromatographic lateral flow platforms and one rapid ELISA system. Leprosy patients were identified with a high degree of sensitivity in each assay (over 80% in all; over 90% among cases with bacterial indices >1+), although critical differences were observed in specificity. While the specificity of CTK OnSite Leprosy Ab Rapid Test and InBios Leprosy Detect™ fast ELISA were high (96.4 and 93.7% in the general population, respectively), there was a marked reduction in OrangeLife NDO-LID® RDT (only 25.0%). As anticipated, seropositivity rates were marginally higher in contacts of leprosy patients than in endemic controls. Although we observed a slight drop in test band intensity when blood, rather than serum, was used to develop OnSite Leprosy Ab Rapid Tests, the sensitivity and specificity of these tests was unaffected. When we contrasted test performance with clinical and bacteriological information, we found that RDT and ELISA results positively correlated with the bacteriological index. These data indicate that these assays could be a ready replacement of invasive, insensitive, and time consuming skin slit smear procedures that additionally require expert microscopic examinations. We propose that, due to their speed and point of care applicability, the RDT could be used as an initial entry point to the diagnostic protocols, with confirmation of results attained in a highly quantitative manner following serum transfer to a reference laboratory.


Asunto(s)
Anticuerpos Antibacterianos/sangre , Cromatografía de Afinidad/métodos , Ensayo de Inmunoadsorción Enzimática/métodos , Lepra Multibacilar/sangre , Lepra Multibacilar/diagnóstico , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Niño , Femenino , Humanos , Lepra Multibacilar/inmunología , Lepra Multibacilar/microbiología , Masculino , Persona de Mediana Edad , Mycobacterium leprae/química , Mycobacterium leprae/inmunología , Sistemas de Atención de Punto , Sensibilidad y Especificidad , Factores de Tiempo
15.
BMC Infect Dis ; 15: 218, 2015 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-26021317

RESUMEN

BACKGROUND: Serological tests can be important tools to assist in the diagnosis of leprosy and can contribute to an earlier diagnosis. The aim of this study was to evaluate the antibody responses against phenolic glycolipid-1 (PGL-1), natural disaccharide linked to human serum albumin via an octyl (NDO-HSA), Leprosy IDRI Diagnostic-1 (LID-1) and natural disaccharide octyl--Leprosy IDRI Diagnostic-1 (NDO-LID) in leprosy patients, household contacts of patients and the general population. METHODS: Enzyme-linked immunosorbent assays were used to analyze the antigen-specific antibody responses of 94 leprosy cases, 104 household contacts of cases and 2.494 individuals from the general population. RESULTS: A positive correlation was observed for the antibody responses to all antigens studied. A higher proportion of seropositivity for all antigens, along with stronger magnitude of response, was observed in multibacillary (MB) leprosy patients and household contacts of MB leprosy patients compared with the levels observed in paucibacillary (PB) leprosy patients and household contacts of PB leprosy patients. A substantial and significant positive correlation was found between seropositivity and the bacterial index for the leprosy patients. Anti-PGL-1 tests were more frequently positive than anti-NDO-HSA tests among patients with all clinical forms of leprosy and among the group of household contacts. The LID-1 and NDO-LID antigens showed a greater capacity to identify household contacts and individuals from the general population infected with M. leprae. CONCLUSIONS: Tests that measure the antibody responses against LID-1, NDO-LID, NDO-HSA and PGL-1 were effective tools for the detection of patients with MB leprosy. Our data indicate that the anti-LID-1 and anti-NDO-LID responses were more effective than an anti-NDO-HSA response for the identification of individuals with subclinical infection.


Asunto(s)
Anticuerpos Antibacterianos/inmunología , Antígenos Bacterianos/inmunología , Lepra Multibacilar/inmunología , Lepra Paucibacilar/inmunología , Mycobacterium leprae/inmunología , Infecciones Asintomáticas , Brasil , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Composición Familiar , Femenino , Glucolípidos/inmunología , Humanos , Lepra/diagnóstico , Lepra/inmunología , Lepra Multibacilar/diagnóstico , Lepra Paucibacilar/diagnóstico , Recuento de Leucocitos , Masculino , Pruebas Serológicas
16.
PLoS One ; 10(5): e0127416, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25992795

RESUMEN

BACKGROUND: Despite the efficacy of multidrug therapy, surviving Mycobacterium leprae causes relapse in some leprosy patients, and these patients present signs and symptoms of disease after healing. This study focused on the cellular immune response in relapsed multibacillary patients but also included non-relapsed multibacillary cured individuals, newly diagnosed and untreated multibacillary patients, paucibacillary patients just before the beginning of treatment, and voluntary healthy individuals for comparative analysis. METHODOLOGY/PRINCIPAL FINDINGS: Inhibition of CD86 expression in the blood-derived monocytes and dendritic cells of relapsed multibacillary patients, either ex vivo or after M. leprae antigen stimulation was observed by flow cytometry. In addition, no significant changes in Interferon-gamma (IFN-g) expression were observed in 5-day culture supernatants of relapsed patients in response to M. leprae, neither before nor after treatment, as measured by ELISA. However, these patients demonstrated a significant increase in central memory CD4+ and CD8+ M. leprae-specific T cells, as assessed by multiparametric flow cytometry. The increase in frequency of central memory T cells in relapsed patients strongly correlated with the bacillary index and the number of skin lesions observed in these subjects. Moreover, cytokine multiplex analysis demonstrated significant antigen-specific production of Interlukin-1beta (IL-1b), IL-6, and Tumour Necrosis Factor (TNF) in the relapsed group with extremely low IL-10 production, which resulted in a high TNF/IL-10 ratio. CONCLUSIONS/SIGNIFICANCE: Inhibition of CD86 expression may function to reduce effector T cell responses against the M. leprae antigen. Furthermore, the predominance of central memory T cells in association with the high TNF/IL-10 ratio and no observed IFN-g production may be related to the pathogenesis of relapse in multibacillary leprosy. Therefore, our findings may be a direct result of the clinical presentation, including a number of skin lesions and bacterial load, of relapsed patients. To our knowledge, this is the first study correlating immune response parameters with the clinical presentation of relapsed multibacillary patients.


Asunto(s)
Citocinas/biosíntesis , Memoria Inmunológica , Mediadores de Inflamación/metabolismo , Lepra Multibacilar/inmunología , Linfocitos T/inmunología , Adolescente , Adulto , Femenino , Humanos , Leprostáticos/uso terapéutico , Lepra Multibacilar/tratamiento farmacológico , Lepra Multibacilar/patología , Masculino , Persona de Mediana Edad , Recurrencia
17.
Lupus ; 24(10): 1095-102, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25761657

RESUMEN

Leprosy is an infectious chronic disease with a wide range of clinical and serological manifestations. We report a case of a woman presenting with a malar rash, painless oral ulcers, photosensitivity, arthritis, positive antinuclear antibodies test and leuko-lymphopenia. Our case illustrates an unusual presentation of leprosy initially diagnosed as systemic lupus erythematosus (SLE). After the confirmation of multibacillary leprosy and multidrug therapy recommended by the World Health Organization, a good clinical response was observed. Recognition of rheumatic manifestations in leprosy is important as they may be confused with SLE. A literature review is presented to encourage clinicians to consider leprosy as a differential diagnosis. Specifically in patients with unusual rheumatic manifestations and persistent skin lesions, and when neurological symptoms are present. Leprosy has not been eradicated, so misdiagnosis can be frequent. It is necessary to increase medical practitioner awareness in order start proper treatment.


Asunto(s)
Lepra Multibacilar/diagnóstico , Lupus Eritematoso Sistémico/diagnóstico , Diagnóstico Diferencial , Errores Diagnósticos , Femenino , Glucocorticoides/uso terapéutico , Humanos , Leprostáticos/uso terapéutico , Lepra Multibacilar/tratamiento farmacológico , Lepra Multibacilar/inmunología , Lepra Multibacilar/patología , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/patología , Persona de Mediana Edad , Mycobacterium leprae/aislamiento & purificación , Resultado del Tratamiento
18.
J Eur Acad Dermatol Venereol ; 29(7): 1354-61, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25429820

RESUMEN

BACKGROUND: Studies on the immunology of leprosy are fundamental to the understanding of the various forms of clinical manifestation of the disease. In some diseases, lymphocytes TH17 and one of its key cytokines, interleukin-17 has been shown to be essential in developing an effective immune response. In leprosy, involvement of lymphocyte TH17 and interleukin-17 remains understudied. OBJECTIVES: This study is the first investigation to examine the association between TH17 cells, interleukin-17 and interferon- γ in patients and households contacts of leprosy. METHODS: To document the participation of TH17 cells and interleukin-17 in the immunology of leprosy, to observe the behavior of interferon-γ in relation to interleukin-17 and to verify the differences found between individuals paucibacillary, multibacillary and household contacts, we analyzed samples peripheral blood to identify TH-17 cells, interleukin-17 and IFN-γ; establishing relationships between all the groups. RESULTS: There was a significant difference in the results found in the comparison between the paucibacillary and multibacillary groups of patients (P < 0.001), as well with the household contacts (P < 0.005). The polychemotherapeutic treatment modified the profile of immune response in multibacillary patients compared to what was observed before the start of treatment. CONCLUSION: The principal finding was that TH17 lymphocytes and interleukin-17 actively participating in the immune response of Hansen's disease as well these cells can stimulate the cellular immunity.


Asunto(s)
Inmunidad Celular , Interferón gamma/inmunología , Interleucina-17/inmunología , Leprostáticos/uso terapéutico , Lepra Multibacilar/inmunología , Lepra Paucibacilar/inmunología , Células Th17/inmunología , Adolescente , Adulto , Anciano , Femenino , Humanos , Interferón gamma/metabolismo , Interleucina-17/metabolismo , Lepra Multibacilar/tratamiento farmacológico , Lepra Multibacilar/transmisión , Lepra Paucibacilar/tratamiento farmacológico , Lepra Paucibacilar/transmisión , Masculino , Persona de Mediana Edad , Adulto Joven
19.
Hansen. int ; 39(2): 70-74, 2014. ilus
Artículo en Portugués | LILACS, Sec. Est. Saúde SP | ID: biblio-831071

RESUMEN

A reação reversa maculosa consiste no aparecimento abrupto de máculas hipocrômicas, ocorrendo em pacientes hansenianos dimorfos que completaram o tratamento com poliquimioterapia para hanseníase multibacilar. Em geral, surgem entre 6 a 12 meses da alta, com baciloscopia negativa e boa resposta a corticoterapia sistêmica. Ressaltamos a dificuldade em diferenciar recidiva de um episódio reacional, já que não existem critérios clínicos bem estabelecidos que possibilitem este diagnóstico, além de existirem poucos relatos em literatura. Relatamos um caso clínico com diagnóstico de reação reversa macular após período variável de alta do tratamento de hanseniase dimorfa-dimorfa. Foi feita investigação por meio de anamnese rigorosa, exame dermatológico, exame histopatológico da lesão e baciloscopia, excluindo-se os critérios de recidiva, além de analisados dados anteriores do prontuário.O paciente foi submetido a corticoterapia sistêmica,apresentando melhora das lesões. Conclui-seque a reação reversa maculosa deve ser lembrada nos diagnósticos diferenciais com hanseníase recidivada e episódios reacionais clássicos, evitando retratamentos desnecessários.


Macular reversal reaction is the abrupt onset of hypochromic lesions, occurring in borderline leprosy patients who completed treatment with multidrugtherapy for multibacillary leprosy. In general, these reactions appear 6 to 12 months after medical discharge, showing negative skin smear and good response to systemic corticosteroid therapy. We emphasize the difficulty in differentiating relapse cases from leprosy reactions, as there are no well-established clinical criteria that allow this diagnosis, and moreover there are few reports about it in the literature. We report a borderline leprosy case diagnosed with macular reversal reaction after variable period of discharge from treatment. Detailed anamnesis, dermatological and histopathological examination and bacilloscopy, analysis of previous medical records, excluding the relapse criteria, were used for the investigation. The patient was submitted to systemic corticosteroid therapy, with improvement of the lesions. It is concluded that macular reversal reaction should be considered in the differential diagnosis of relapsed leprosy and classic reactional episodes, avoiding unnecessary retreatment.


Asunto(s)
Humanos , Masculino , Adulto , Lepra Multibacilar/complicaciones , Lepra Multibacilar/inmunología , Inmunidad Celular/inmunología , Lepra Multibacilar , Inducción de Remisión , Quimioterapia , Quimioterapia Combinada
20.
PLoS One ; 8(11): e79072, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24244424

RESUMEN

BACKGROUND: Leprosy is a chronic disease, caused by Mycobacterium leprae, which poses a serious public health problem worldwide. Its high incidence in people under 15 years old in Ceará state, Brazil, reflects the difficulty of its control. The spectrum of clinical manifestations is associated with the immune response developed, with the Th1 and Th2 responses being related to the paucibacillary and multibacillary forms, respectively. Regulatory T cells (Treg), which can suppress Th1 and Th2 response, have received special attention in the literature and have been associated with development of chronic infections. However, their role in leprosy in individuals under 15 years old has not yet been elucidated. We evaluated the frequency of CD4(+)/CD8(+)CD25(high)FOXP3(+) and CD4(+)/CD8(+)CD25(high)FOXP3(high) cells in leprosy patients and household contacts, in both cases under 15 years old. METHODOLOGY/PRINCIPAL FINDINGS: PBMC from 12 patients and 17 contacts were cultured for 72 hours with anti-CD3 and anti-CD28 (activators) or with activators associated with total sonicated fraction of M. leprae. After culture, the frequency of CD4(+)/CD8(+) Treg was identified by flow cytometry. Cells stimulated by activators and antigen from multibacillary patients showed Treg frequencies almost two times that of the contacts: CD4(+)FOXP3(+) (21.93±8.43 vs. 13.79±8.19%, p = 0.0500), CD4(+)FOXP3(high) (10.33±5.69 vs. 5.57±4.03%, p = 0.0362), CD8(+)FOXP3(+) (13.88±9.19 vs. 6.18±5.56%, p = 0.0230) and CD8(+)FOXP3(high) (5.36±4.17 vs. 2.23±2.68%, p = 0.0461). Furthermore, the mean fluorescence intensity of FOXP3 in Treg was higher in multibacillary patients than in the contacts. Interestingly, there was a positive correlation of the bacillary index and number of lesions with the frequency of all Treg evaluated in patients. CONCLUSIONS/SIGNIFICANCE: We have demonstrated for the first time that multibacillary leprosy patients under 15 years old have greater CD4(+) and CD8(+) Treg frequencies and these correlate with clinical and laboratorial aspects of disease. These findings suggest the involvement of these cells in the perpetuation of M. leprae infection.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Lepra Multibacilar/inmunología , Mycobacterium leprae/inmunología , Linfocitos T Reguladores/inmunología , Adolescente , Recuento de Linfocito CD4 , Linfocitos T CD8-positivos/patología , Células Cultivadas , Niño , Preescolar , Femenino , Humanos , Lepra Multibacilar/patología , Masculino , Linfocitos T Reguladores/patología
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