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1.
Am J Dermatopathol ; 40(3): 205-208, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28937434

RESUMEN

BACKGROUND: Dapsone hypersensitivity syndrome (DHS) is a rare, but potentially life-threatening reaction to dapsone. OBJECTIVE: Evaluation of immunological factors involved in the sparing of borderline-lepromatous (BL) leprosy patches by the severe exanthema related to DHS. METHODS: The authors describe a 19-year-old man with borderline-lepromatous leprosy with a recent diffuse rash, sparing only the hypochromic patches of leprosy, generalized lymphadenopathy, hepatomegaly, and jaundice 25 days after the start of multibacillary multidrug therapy. RESULTS: Laboratory testing was remarkable for leukocytosis with eosinophilia, atypical lymphocytosis, and elevated liver and canalicular enzymes. Immunohistopathology of the rash showed stronger expression of Th1 cytokines (IL1ß, TNFα, IFNγ, and iNOS), and limited expression of IL17, TGFb, IL4, and IL10. Whereas the hypochromic leprosy patches showed high expression of inflammatory cytokines IL1ß, TNFα, IFNγ, iNOS, and TGFß (Th1), and presented strong expression of IL17 and TGFß with no IL4 and IL10 expression, by the inflammatory infiltrate, characterizing a participation of Th17 response. CONCLUSION: Th17 response, coupled with the presence of subepidermal collagen band, seems to be directly related to the absence of DHS rash in these hypochromic leprosy patches.


Asunto(s)
Dapsona/efectos adversos , Síndrome de Hipersensibilidad a Medicamentos/inmunología , Leprostáticos/efectos adversos , Lepra Dimorfa/tratamiento farmacológico , Células Th17/inmunología , Síndrome de Hipersensibilidad a Medicamentos/etiología , Humanos , Lepra Dimorfa/inmunología , Masculino , Adulto Joven
2.
BMC Dermatol ; 17(1): 16, 2017 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-29262820

RESUMEN

BACKGROUND: Erythroderma is characterized by erythema and scaling affecting more than 90% of the body surface area. Inflammatory, neoplastic and, more rarely, infectious diseases may culminate with erythroderma. Diagnosis of the underlying disorder is therefore crucial to institute the appropriate therapy. Leprosy is a chronic infectious disease that is endemic in Brazil. Here we present an unusual case of leprosy and reversal reaction causing erythroderma, and we discuss the underlying immunological mechanisms which could contribute to the generalized skin inflammation. CASE PRESENTATION: We report a case of a patient with reversal reaction (RR) in borderline borderline leprosy presenting with erythroderma and neural disabilities. Histopathology of the skin showed regular acanthosis and spongiosis in the epidermis and, in the dermis, compact epithelioid granulomas as well as grouped and isolated bacilli. This duality probably reflects the transition from an anergic/multibacillary state to a state of more effective immunity and bacillary control, typical of RR. Leprosy was successfully treated with WHO's multidrug therapy, plus prednisone for controlling the RR; the erythroderma resolved in parallel with this treatment. Immunologic studies showed in situ predominance of IFNγ + over IL-4+ lymphocytes and of IL-17+ over Foxp3+ lymphocytes, suggesting an exacerbated Th-1/Th-17 immunoreactivity and poor Th-2 and regulatory T-cell responses. Circulating Tregs were also diminished. We hypothesize that the flare-up of anti-mycobacteria immunoreactivity that underlies RR may have triggered the intense inflammatory skin lesions that culminated with erythroderma. CONCLUSIONS: This case report highlights the importance of thorough clinical examination of erythrodermic patients in search for its etiology and suggests that an intense and probably uncontrolled leprosy RR can culminate in the development of erythroderma.


Asunto(s)
Dermatitis Exfoliativa/etiología , Lepra Dimorfa/complicaciones , Piel/patología , Antiinflamatorios/uso terapéutico , Biopsia , Dermatitis Exfoliativa/tratamiento farmacológico , Dermatitis Exfoliativa/patología , Quimioterapia Combinada , Humanos , Interferón gamma/metabolismo , Leprostáticos/uso terapéutico , Lepra Dimorfa/tratamiento farmacológico , Lepra Dimorfa/inmunología , Linfocitos/metabolismo , Masculino , Persona de Mediana Edad , Prednisolona/uso terapéutico , Linfocitos T Reguladores/inmunología
3.
J Dtsch Dermatol Ges ; 15(8): 801-827, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28763601

RESUMEN

Leprosy is a chronic infectious disease caused by Mycobacterium (M.) leprae. Worldwide, 210,758 new cases were diagnosed in 2015. The highest incidence is found in India, Brazil, and Indonesia. While the exact route of transmission remains unknown, nasal droplet infection is thought to be most likely. The pathogen primarily affects the skin and peripheral nervous system. The disease course is determined by individual host immunity. Clinically, multibacillary lepromatous variants are distinguished from paucibacillary tuberculoid forms. Apart from the various characteristic skin lesions, the condition is marked by damage to the peripheral nervous system. Advanced disease is characterized by disfiguring mutilations. Current treatment options are based on WHO recommendations. Early treatment frequently results in complete remission without sequelae. While paucibacillary forms are treated with rifampicin and dapsone for at least six months, multibacillary leprosy is treated for at least twelve months, additionally requiring clofazimine. Leprosy reactions during therapy may considerably aggravate the disease course. Besides individual treatment, WHO-supported preventive measures and strategies play a key role in endemic areas.


Asunto(s)
Leprostáticos/uso terapéutico , Lepra Lepromatosa/diagnóstico , Lepra Lepromatosa/tratamiento farmacológico , Lepra Tuberculoide/diagnóstico , Lepra Tuberculoide/tratamiento farmacológico , Enfermedades Desatendidas , Adulto , Anciano , Niño , Clofazimina/efectos adversos , Clofazimina/uso terapéutico , Estudios Transversales , Dapsona/efectos adversos , Dapsona/uso terapéutico , Progresión de la Enfermedad , Esquema de Medicación , Femenino , Adhesión a Directriz , Humanos , Inmunidad Celular/efectos de los fármacos , Lepra Dimorfa/diagnóstico , Lepra Dimorfa/tratamiento farmacológico , Lepra Dimorfa/epidemiología , Lepra Dimorfa/inmunología , Lepra Lepromatosa/epidemiología , Lepra Lepromatosa/inmunología , Lepra Tuberculoide/epidemiología , Lepra Tuberculoide/inmunología , Cuidados a Largo Plazo , Masculino , Rifampin/efectos adversos , Rifampin/uso terapéutico
4.
PLoS Negl Trop Dis ; 10(8): e0004955, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27556927

RESUMEN

Erythema Nodosum Leprosum (ENL) is an immune reaction in leprosy that aggravates the patient´s clinical condition. ENL presents systemic symptoms of an acute infectious syndrome with high leukocytosis and intense malaise clinically similar to sepsis. The treatment of ENL patients requires immunosuppression and thus needs to be early and efficient to prevent both disabilities and permanent nerve damage. Some patients experience multiple episodes of ENL and prolonged use of immunosuppressive drugs may lead to serious adverse effects. Thalidomide treatment is extremely effective at ameliorating ENL symptoms. Several mechanisms have been proposed to explain the efficacy of thalidomide in ENL, including the inhibition of TNF production. Given its teratogenicity, thalidomide is prohibitive for women of childbearing age. A rational search for molecular targets during ENL episodes is essential to better understand the disease mechanisms involved, which may also lead to the discovery of new drugs and diagnostic tests. Previous studies have demonstrated that IFN-γ and GM-CSF, involved in the induction of CD64 expression, increase during ENL. The aim of the present study was to investigate CD64 expression during ENL and whether thalidomide treatment modulated its expression. Leprosy patients were allocated to one of five groups: (1) Lepromatous leprosy, (2) Borderline leprosy, (3) Reversal reaction, (4) ENL, and (5) ENL 7 days after thalidomide treatment. The present study demonstrated that CD64 mRNA and protein were expressed in ENL lesions and that thalidomide treatment reduced CD64 expression and neutrophil infiltrates-a hallmark of ENL. We also showed that ENL blood neutrophils exclusively expressed CD64 on the cell surface and that thalidomide diminished overall expression. Patient classification based on clinical symptoms found that severe ENL presented high levels of neutrophil CD64. Collectively, these data revealed that ENL neutrophils express CD64, presumably contributing to the immunopathogenesis of the disease.


Asunto(s)
Eritema Nudoso/inmunología , Leprostáticos/uso terapéutico , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Receptores de IgG/genética , Talidomida/uso terapéutico , Adolescente , Adulto , Anciano , Biopsia , Eritema Nudoso/diagnóstico , Eritema Nudoso/tratamiento farmacológico , Eritema Nudoso/microbiología , Femenino , Humanos , Lepra Dimorfa/tratamiento farmacológico , Lepra Dimorfa/inmunología , Lepra Dimorfa/microbiología , Lepra Lepromatosa/tratamiento farmacológico , Lepra Lepromatosa/inmunología , Lepra Lepromatosa/microbiología , Masculino , Persona de Mediana Edad , Receptores de IgG/inmunología , Piel/microbiología , Piel/patología , Adulto Joven
5.
BMC Infect Dis ; 15: 22, 2015 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-25605482

RESUMEN

BACKGROUND: Evidence suggests that human leukocyte antigen (HLA) alleles influence the host immune response against Mycobacterium leprae. However, the association between HLA alleles and borderline (B) leprosy has not been studied. The aim of this study was to determine whether HLA class I and II molecules are associated with susceptibility or resistance to B leprosy including borderline-tuberculoid (BT), borderline-borderline (BB), and borderline-lepromatous (BL). METHODS: DNA was obtained by the salting-out technique from the blood samples of 202 patients with B leprosy and 478 control subjects. HLA class I (A*, B*, and C* loci) and class II (DRB1* and DQB1* loci) genotypes were determined by polymerase chain reaction amplification and reverse hybridization with sequence-specific oligonucleotide probes and sequence-specific primers. RESULTS: The case-controlled analysis results showed a significant association between B leprosy and HLA-C*05 (5.94% vs. 14.02%; p = 0.002, OR = 0.38, 95% CI = 0.20-0.73, pc = 0.032) and HLA-DRB1*07 (16.34% vs. 26.77%; p = 0.003, OR = 0.53, 95% CI = 0.3-0.8, pc = 0.039). A protective association was observed between BL leprosy and HLA-DQB1*02 (18.18% vs. 39.53%; p = 0.005, OR = 0.34, 95% CI = 0.15-0.75, pc = 0.025). In reactional patients, a significant association was observed between HLA-B*15 (28.72% vs. 12.76%; p = 0.011, OR = 2.75, 95% CI = 1.30-5.85, pc = 0.352) and predisposition to reversal reaction. Haplotype analysis showed that A*02-B*07-C*07-DRB1*15-DQB1*06 (2.97% vs. 1.04%; p = 0.015) and A*02-B*40-C*03-DRB1*13-DQB1*06 (1.73% vs. 0.10%; p = 0.0011) were associated with susceptibility to the B form. The presence of the HLA-DRB1*02 or HLA-DRB1*03/HLA-DQB1*01 haplotypes in B patients (22.05% vs. 33.0%; p = 0.005) suggested the involvement of these haplotypes in this clinical form of the disease. CONCLUSIONS: The results indicate the involvement of HLA class I and class II molecules in B leprosy and reversal reactions; it also suggest a role for HLA in polarization of the disease in this group of patients.


Asunto(s)
Predisposición Genética a la Enfermedad , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Lepra Dimorfa/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Brasil , Estudios de Casos y Controles , Niño , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Lepra Dimorfa/inmunología , Masculino , Persona de Mediana Edad , Mycobacterium leprae/inmunología , Reacción en Cadena de la Polimerasa , Adulto Joven
6.
s.l; s.n; 2015. 9 p. tab.
No convencional en Inglés | Sec. Est. Saúde SP, HANSEN, SESSP-ILSLPROD, Sec. Est. Saúde SP, SESSP-ILSLACERVO, Sec. Est. Saúde SP | ID: biblio-1095298

RESUMEN

BACKGROUND: Evidence suggests that human leukocyte antigen (HLA) alleles influence the host immune response against Mycobacterium leprae. However, the association between HLA alleles and borderline (B) leprosy has not been studied. The aim of this study was to determine whether HLA class I and II molecules are associated with susceptibility or resistance to B leprosy including borderline-tuberculoid (BT), borderline-borderline (BB), and borderline-lepromatous (BL). METHODS: DNA was obtained by the salting-out technique from the blood samples of 202 patients with B leprosy and 478 control subjects. HLA class I (A*, B*, and C* loci) and class II (DRB1* and DQB1* loci) genotypes were determined by polymerase chain reaction amplification and reverse hybridization with sequence-specific oligonucleotide probes and sequence-specific primers. RESULTS: The case-controlled analysis results showed a significant association between B leprosy and HLA-C*05 (5.94% vs. 14.02%; p = 0.002, OR = 0.38, 95% CI = 0.20-0.73, pc = 0.032) and HLA-DRB1*07 (16.34% vs. 26.77%; p = 0.003, OR = 0.53, 95% CI = 0.3-0.8, pc = 0.039). A protective association was observed between BL leprosy and HLA-DQB1*02 (18.18% vs. 39.53%; p = 0.005, OR = 0.34, 95% CI = 0.15-0.75, pc = 0.025). In reactional patients, a significant association was observed between HLA-B*15 (28.72% vs. 12.76%; p = 0.011, OR = 2.75, 95% CI = 1.30-5.85, pc = 0.352) and predisposition to reversal reaction. Haplotype analysis showed that A*02-B*07-C*07-DRB1*15-DQB1*06 (2.97% vs. 1.04%; p = 0.015) and A*02-B*40-C*03-DRB1*13-DQB1*06 (1.73% vs. 0.10%; p = 0.0011) were associated with susceptibility to the B form. The presence of the HLA-DRB1*02 or HLA-DRB1*03/HLA-DQB1*01 haplotypes in B patients (22.05% vs. 33.0%; p = 0.005) suggested the involvement of these haplotypes in this clinical form of the disease. CONCLUSIONS: The results indicate the involvement of HLA class I and class II molecules in B leprosy and reversal reactions; it also suggest a role for HLA in polarization of the disease in this group of patients.


Asunto(s)
Humanos , Masculino , Femenino , Niño , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Adulto Joven , Brasil , Lepra Dimorfa/genética , Lepra Dimorfa/inmunología , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Estudios de Casos y Controles , Reacción en Cadena de la Polimerasa , Predisposición Genética a la Enfermedad , Alelos , Frecuencia de los Genes , Genotipo , Mycobacterium leprae/inmunología
7.
Lepr Rev ; 85(1): 54-7, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24974443

RESUMEN

The liver is the most frequently affected visceral organ in leprosy, particularly in the multibacillary group. Administration of hepatotoxic drugs may also affect liver function. We report the case of a male patient, diagnosed as borderline lepromatous leprosy with Type 2 reaction, who was managed with multibacillary multidrug therapy and steroids, and who then developed acute hepatitis and succumbed to sudden cardiac death. Although erythema nodosum leprosum has been described as a rare cause of death in the literature, such an occurrence in the present era when leprosy has been eliminated needs a special mention.


Asunto(s)
Lepra Dimorfa/complicaciones , Lepra Lepromatosa/complicaciones , Fallo Hepático Agudo/etiología , Adolescente , Resultado Fatal , Humanos , Lepra Dimorfa/inmunología , Lepra Lepromatosa/inmunología , Fallo Hepático Agudo/diagnóstico , Fallo Hepático Agudo/mortalidad , Masculino
8.
Int J Dermatol ; 53(1): 61-5, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23675902

RESUMEN

BACKGROUND: Lepromatous leprosy is associated with suppressed cell-mediated immunity (CMI). This results in failure of the body to mount an efficient immune response and may render chemotherapy ineffective. The lack of sufficient response may mimic drug resistance. Three case reports in which the immunity was stimulated by administering Injection BCG are presented. All three patients were initially anergic and showed no reaction at the Mantoux testing site, showing an inability to mount type IV hypersensitivity and characterized by live bacilli in smears. Following 1-4 doses of Injection BCG, all three showed dead bacilli in smears. CASE REPORTS: The first case, a 61-year-old man with lepromatous leprosy who continued to show live bacilli in smears after prolonged chemotherapy, was administered a total of four BCG injections, following which he achieved clearance. The second, a 40-year-old man with borderline lepromatous leprosy and severe type 2 reactions, achieved bacterial clearance and control of severe reactions following a single injection. The third, a 67-year-old man with histoid leprosy, achieved effective bacterial killing with a single dose of Injection BCG. RESULTS: All three patients achieved good results when chemotherapy was combined with Injection BCG. Following Injection BCG, all three showed a reaction at the Mantoux testing site. CONCLUSIONS: Suppressed CMI may be responsible for the lack of response in recalcitrant cases of lepromatous leprosy. These case reports would lead to the trend in combination therapy (immunotherapy combined with chemotherapy) for such cases, and help lower the tendency for inappropriate diagnosis of drug-resistant leprosy.


Asunto(s)
Vacuna BCG/uso terapéutico , Inmunidad Celular/inmunología , Leprostáticos/administración & dosificación , Lepra Lepromatosa/tratamiento farmacológico , Lepra Lepromatosa/inmunología , Mycobacterium leprae/efectos de los fármacos , Adulto , Anciano , Farmacorresistencia Bacteriana , Humanos , Leprostáticos/efectos adversos , Lepra Dimorfa/tratamiento farmacológico , Lepra Dimorfa/inmunología , Lepra Dimorfa/patología , Lepra Lepromatosa/patología , Masculino , Persona de Mediana Edad , Mycobacterium leprae/inmunología
9.
J Clin Immunol ; 32(6): 1415-20, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22847545

RESUMEN

PURPOSE: Leprosy is a chronic infectious disease caused by Mycobacterium leprae affecting mainly skin and peripheral nerves. Acute inflammatory episodes in the borderline immunological spectrum of the disease cause severe nerve and tissue damage leading to deformities. Finding of any serological marker for leprosy reactions will help in prediction of reactions and in early treatment intervention. The objective of this study was to measure the serum circulatory levels of Interleukin 17F (IL 17F) and to correlate the levels with type 1 and type 2 reactional states and with clinico-histopathological spectrum of leprosy. We studied IL 17F to delineate its role and its clinical implications in leprosy reactions. METHODS: Patients were classified based on the Ridley DS and Jopling WH Classification and blood samples (5 ml each) were collected from 80 active untreated leprosy cases in Type 1 reaction (T1R), 21 cases in Type 2 (Erythema Nodosum Leprosum ENL) reaction (T2R), 80 cases without reaction (NR), and 94 non-leprosy cases (NL). Serum was separated and measured for IL 17F levels using ELISA (Commercial Kits, R&D Systems Inc., USA). RESULTS: IL 17F levels were significantly higher in the T1R group when compared to the NR group (p < 0.001). The borderline lepromatous group showed the highest levels of IL 17F among the other groups in the disease spectrum. Bacteriological index (BI) showed negative correlation with the IL 17F levels. CONCLUSION: The results specify that serum circulatory levels of IL 17F are elevated during T1Rs in the borderline spectrum of the disease and thus may play a role in the regulation of inflammatory responses associated with reactions in leprosy.


Asunto(s)
Eritema Nudoso/sangre , Interleucina-17/sangre , Lepra Dimorfa/sangre , Lepra Lepromatosa/sangre , Mycobacterium leprae/fisiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Estudios de Casos y Controles , Niño , Ensayo de Inmunoadsorción Enzimática , Eritema Nudoso/inmunología , Eritema Nudoso/patología , Femenino , Humanos , Interleucina-17/inmunología , Lepra Dimorfa/inmunología , Lepra Dimorfa/patología , Lepra Lepromatosa/inmunología , Lepra Lepromatosa/patología , Masculino , Persona de Mediana Edad
10.
Indian J Lepr ; 84(4): 287-306, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23720894

RESUMEN

This study reports detailed analysis of clinical parameters and clearance of granuloma in borderline leprosy patients treated with immunotherapy and chemotherapy. It aims to assess the additive effect of immunotherapy (Mwvaccine) with standard MDT on clinical status of untreated borderline leprosy cases and on granuloma fraction of untreated borderline leprosy cases. Patients attending the OPD were serially recruited in two groups. A total of 150 cases in one treatment (trial) group (Mw vaccine plus MDT) and 120 cases in another treatment (control) group (MDT only) of border line leprosy have been included. After the formal written consent, detailed clinical examination, charting, smear examination of all untreated borderline patients of both groups was done, biopsies were taken from the active lesions of all patients of both groups at start of therapy and every six month thereafter till the completion of therapy. The same procedure was repeated every six months during the follow-up period. Standard MDT was given to all the patients of both groups according to type of disease. Mw vaccine 0.1 ml (0.5 x 10(9) bacilli) was injected intra-dermally at the start of therapy and every six months in addition to chemotherapy to the treatment group. The BT cases were followed up after 6 doses of MDT and 2 doses of Mw vaccine, and, the BB, BL cases were followed up after 24 doses of MDT plus 5 doses of Mw vaccine. Clinically, greater and faster improvement was observed in all the clinical parameters, faster attainment of smear negativity and two episodes of lepra reaction occurred in cases treated with combined chemotherapy and immunotherapy, as compared to controls (chemotherapy alone) wherein clinical improvement was slower in all parameters, slower attainment of smear negativity in bacillary index and seven showed the occurrence of reactions, histipathologically in addition to more rapid clearance of granuloma in immunotherapy treated group, a significant finding was an increase in the epithelioid cells population in this group. This suggests a possible immunoactivation of the macrophages especially in BB/BL immunotherapy group. Overall comparison of regression induced by chemotherapy alone with that induced by combined chemotherapy and immunotherapy shows a greater reduction in clinical parameters as well as granuloma fraction in BT cases as well as in BB/BL cases. This trial shows the potential usefulness of this approach of addition of immunotherapy to standard chemotherapy in borderline leprosy cases which leads to in faster recovery from disease reduced chances of reactions and faster granuloma clearance. Such information is expected to be useful in improving the immunotherapeutic approaches for treatinggranulomatous conditions in general and in leprosy in particular.


Asunto(s)
Vacunas Bacterianas/administración & dosificación , Inmunoterapia , Leprostáticos/administración & dosificación , Lepra Dimorfa/terapia , Piel/patología , Adolescente , Adulto , Vacunas Bacterianas/efectos adversos , Biopsia , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Granuloma/patología , Granuloma/terapia , Humanos , India , Lepra Dimorfa/clasificación , Lepra Dimorfa/inmunología , Lepra Dimorfa/patología , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven
12.
Med Mal Infect ; 41(7): 390-1, 2011 Jul.
Artículo en Francés | MEDLINE | ID: mdl-21458936
14.
Indian J Lepr ; 81(2): 75-9, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-20509336

RESUMEN

The transmission of leprosy has been universally accepted to be primarily, through nasal dissemination from multibacillary patients to the susceptible persons. However, the possibility of leprosy transmission through prolonged skin contact with abraded leprous skin or through skin inoculation can not be ruled out. We report a case of development of a paucibacillary leprosy patch close to the site of a local trauma, after an interval of about 13-14 years, in a HIV positive subject. Also discussed are the various hypotheses in the aetiopathogenesis of leprosy like entry route of lepra bacilli into the body, viability of lepra bacilli in the environment and evolution of skin and nerve lesions of leprosy.


Asunto(s)
Terapia Antirretroviral Altamente Activa/efectos adversos , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Síndrome Inflamatorio de Reconstitución Inmune/inducido químicamente , Lepra Dimorfa/etiología , Infecciones Oportunistas Relacionadas con el SIDA/inmunología , Infecciones por VIH/complicaciones , Infecciones por VIH/inmunología , Humanos , Lepra Dimorfa/inmunología , Lepra Dimorfa/patología , Masculino , Persona de Mediana Edad , Piel/patología
17.
Botucatu; s.n; 2008. 180 p. ilus, tab, graf.
Tesis en Portugués | Hanseníase | ID: han-25642

RESUMEN

Visando contribuir para o melhor entendimento da participação das citocinas na hanseníase dimorfa, o presente estudo investigou a produção desses mediadores in vitro e in situ em pacientes dimorfos-tuberculóides (HDT) e dimorfos-virchovianos(HDV). Foram avaliados 7 pacientes HDT e 12 HDV, virgens de tratamento, além de 19 indivíduos sádios (grupo controle). Culturas de células mononucleares do sangue periférico (PBMC) foram estimuladas ou não com estímulos inespecíficos e específicos do M. Leprae (antígeno inteiro e sonicado) e após 48 horas o sobrenadante foi recolhido para dosagens das citocinas TNF-a, IFN-y, IL-10 e TGF-B1. Biópsias das lesões cutâneas foram submetidas aos procedimentos histológicos por meio da coloração com hematoxilina-Eosina e Faraco-Fite; os cortes foram submetidos, ainda, à detecção in situ de iNOS, IL-10 e TGF-B1 por imunoistoquímica. A quantificação de citocinas em sobrenadante de PBMC revelou que pacientes HDT produziram níveis menores de TGF-B1 e pacientes HDV, níveis menores de IL-10...(AU)


Asunto(s)
Humanos , Lepra Dimorfa/inmunología , Lepra Dimorfa/patología , Técnicas de Cultivo de Célula/métodos , Citocinas/biosíntesis , Citocinas/inmunología , Interleucina-10/biosíntesis , Interleucina-10/inmunología
18.
Trop Med Int Health ; 12(12): 1450-8, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18076551

RESUMEN

OBJECTIVE: To verify the validity of measuring the levels of Mycobacterium leprae-specific anti-phenolic glycolipid (PGL)-I antibody, neopterin, a product of activated macrophages, and C-reactive protein (CRP), an acute phase protein, in serial serum samples from patients for monitoring the leprosy spectrum and reactions during the course of multi-drug treatment (MDT). METHODS: Twenty-five untreated leprosy patients, 15 multi-bacillary (MB) and 10 paucibacillary (PB), participated. Eight patients developed reversal reaction and five developed erythema nodosum leprosum (ENL) during follow-up. The bacterial index (BI) in slit-skin smears was determined at diagnosis and blood samples collected by venipuncture at diagnosis and after 2, 4, 6 and 12 months of MDT. PGL-I antibody and neopterin were measured by enzyme-linked immunosorbent assay, whereas the CRP levels were measured by the latex agglutination method. RESULTS: The levels of PGL-I antibodies and neopterin were higher in the sera of MB than PB patients, which correlated with the patients' BI. The serum levels of CRP did not differ significantly between the MB and PB patients. The serum levels of PGL-I and neopterin were no higher in reactional patients than non-reactional patients prone to such reactions. However, ENL patients had higher serum CRP levels than non-reactional MB patients. The serum PGL-I antibody levels declined significantly during MDT, in contrast to neopterin and CRP levels. CONCLUSION: Measuring the serum levels of PGL-I antibodies and neopterin appeared to be useful in distinguishing MB from PB patients, whereas monitoring the levels of PGL-I antibodies appeared to be useful in monitoring MB patients on MDT. Measuring serum CRP, although not useful in monitoring the patients, has limited significance in detecting ENL reactional patients.


Asunto(s)
Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/inmunología , Proteína C-Reactiva/metabolismo , Glucolípidos/inmunología , Lepra Dimorfa/sangre , Lepra Tuberculoide/sangre , Neopterin/sangre , Adulto , Anciano , Femenino , Humanos , Leprostáticos/efectos adversos , Leprostáticos/uso terapéutico , Lepra Dimorfa/tratamiento farmacológico , Lepra Dimorfa/inmunología , Lepra Tuberculoide/tratamiento farmacológico , Lepra Tuberculoide/inmunología , Masculino , Persona de Mediana Edad
19.
Br J Dermatol ; 157(2): 273-83, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17553031

RESUMEN

BACKGROUND: Leprosy is characterized by a disease spectrum having two polar clinical forms dependent on the presence or not of cell-mediated immunity. In the tuberculoid forms, granuloma-activated macrophages kill Mycobacterium leprae in conjunction with a Th1 response while, in multibacillary (MB) lesions, M. leprae nonactivated macrophages infiltrate the nerves and internal organs together with a Th2 response. The functional properties and activation pathways of macrophages isolated from patients with MB leprosy remain only partially understood. OBJECTIVES: To establish an ex vivo methodology capable of evaluating the activation pathways, grade and fate of cultured macrophages isolated from MB lesions. METHODS: Skin biopsies from patients with borderline tuberculoid, bordeline lepromatous and lepromatous leprosy (LL) were characterized by immunohistochemistry and transcriptional analysis. To isolate inflammatory cells, a portion of the samples was submitted to enzymatic digestion. These same cells, maintained in culture for a minimum 7-day period, were characterized morphologically and via flow cytometry at different culture time points. Cytokine [interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha and interleukin (IL)-10] mRNA levels were quantified by real-time polymerase chain reaction and protein secretion in the culture supernatants was measured by enzyme-linked immunosorbent assay and the nitric oxide levels by Griess reagent. RESULTS: RNA expression in tuberculoid and MB lesions showed the profile expected of characteristic Th1 and Th2 responses, respectively. The inflammatory cells in all biopsies were successfully isolated. Although the number of cells varied between biopsies, it was highest in LL biopsies. The frequency of isolated CD14+ and CD3+ cells measured by flow cytometry correlated with the percentages of macrophages and lymphocytes in the lesions. Throughout the culture period, CD68+ macrophages showed morphological changes. A progressive increase in cell number and reduction of infected cells were perceptible in the cultures. In contrast to the biopsies, TNF-alpha, IFN-gamma and IL-10 expression in the tuberculoid and MB leprosy cells in 24-h culture and the cytokine levels in the supernatants did not differ significantly. During the culture period, cytokine expression in the MB cells progressively declined, whereas, from days 1 to 7, nitrite levels progressively increased. After day 40, the remaining macrophages were able to ingest fluorescein isothiocyanate-labelled M. leprae. These data need to be confirmed. CONCLUSIONS: This study confirmed the feasibility of obtaining ex vivo macrophages from leprosy lesions and keeping them in long-term culture. This procedure may open new pathways to studying the interaction between M. leprae and human macrophages, which might, in turn, lead to the development of therapeutic tools capable of overcoming the specific anergy found in patients with MB leprosy.


Asunto(s)
Lepra/inmunología , Macrófagos/inmunología , Mycobacterium leprae/fisiología , Piel/inmunología , Adulto , Anciano , Recuento de Células , Células Cultivadas , Citocinas/biosíntesis , Citocinas/genética , Estudios de Factibilidad , Femenino , Expresión Génica , Humanos , Lepra Dimorfa/inmunología , Lepra Lepromatosa/inmunología , Lepra Tuberculoide/inmunología , Macrófagos/parasitología , Masculino , Persona de Mediana Edad , Modelos Biológicos , Nitritos/metabolismo , Fagocitosis/inmunología , ARN Mensajero/genética , Piel/parasitología
20.
Immunol Lett ; 109(1): 72-5, 2007 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-17320974

RESUMEN

Regulation of inflammation in leprosy may be influenced by local concentrations of active cortisol and inactive cortisone, whose concentrations are regulated by enzymes in the cortisol-cortisone shuttle. We investigated the cortisol-cortisone shuttle enzymes in the skin of leprosy patients with type 1 reactions (T1R), which are characterised by skin and nerve inflammation. Gene expression of the shuttle enzymes were quantified in skin biopsies from 15 leprosy patients with new T1R before and during prednisolone treatment and compared with levels in skin biopsies from 10 borderline leprosy patients without reactions. Gene expression of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 2, which converts cortisol to cortisone, is down-regulated in skin from T1R lesions. However expression levels of 11beta-HSD type 1, which converts cortisone to cortisol, were similar in skin with and without reactions and did not change during anti-leprosy drug treatment. Prednisolone treatment of patients with reactions is associated with an upregulation of 11beta-HSD2 expression in skin. The down regulation of 11beta-HSD2 at the beginning of a reaction may be caused by pro-inflammatory cytokines in the leprosy reactional lesion and may be a local attempt to down-regulate inflammation. However in leprosy reactions this local response is insufficient and exogenous steroids are required to control inflammation.


Asunto(s)
Cortisona/metabolismo , Hidrocortisona/metabolismo , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/biosíntesis , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/genética , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/metabolismo , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2/biosíntesis , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2/genética , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2/metabolismo , Cortisona/inmunología , Expresión Génica , Humanos , Hidrocortisona/inmunología , India , Lepra Dimorfa/genética , Lepra Dimorfa/inmunología , Lepra Dimorfa/metabolismo , Lepra Dimorfa/microbiología , Prednisolona/inmunología
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