RESUMEN
It is well documented that sporadic Alzheimer's disease (AD) is a multifactorial disease and considered to be a result of several pathological events, both in the periphery and in the brain. The role of the peripheral immune system in the etiology and/or progression of the disease is not fully understood yet, and the results in humans are contradictory so far. Several animal models of AD have been generated and thoroughly characterized to elucidate disease mechanisms and evaluate numerous therapeutic strategies in preclinical studies. In the present study, we carried out a longitudinal evaluation of blood lymphocytes from male and female 3xTg-AD mice to document important immunological abnormalities in the periphery. We documented the age-dependent decrease in the percentage of CD3+ and CD4+ lymphocytes and an increase in the percentage CD3+CD4-CD8- (DN T) cells in the blood of 3xTg-AD mice compared with non-transgenic animals. Severe splenomegaly was observed in 3xTg-AD mice in contrast to wild-type animals. Importantly, all these abnormalities in the peripheral immune system appeared earlier and were more pronounced in males compared with females of the same age, which may account for the shorter lifespan of male mice. We suggest that future research should include the measurement of CD3+ and DN T cells as a potential immunological marker of disease progression in AD patients.
Asunto(s)
Envejecimiento/inmunología , Enfermedad de Alzheimer/inmunología , Recuento de Linfocitos , Caracteres Sexuales , Subgrupos de Linfocitos T/inmunología , Envejecimiento/sangre , Enfermedad de Alzheimer/sangre , Animales , Complejo CD3/análisis , Antígenos CD4/análisis , Antígenos CD8/análisis , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Ratones , Ratones Transgénicos , Subgrupos de Linfocitos T/químicaRESUMEN
We aimed to investigate the effects of ethanol and its metabolites (ß-hydroxybutyrate and sodium acetate) in the effector functions of macrophages in response to Paracoccidioides brasiliensis yeast cells and to determine their influence in the development of the adaptive response. Purified peripheral blood monocytes were differentiated into macrophages and were treated with ethanol, ß-hydroxybutyrate, and sodium acetate, and stimulated with P. brasiliensis yeast cells and evaluated for their phenotypic characteristics, functional activity, and capability to induce T cells activation/differentiation. We found that the ethanol treatment diminished the expression of HLA-AB, HLA-DR, CD80, and CD86, modulating the expression of dectin-1, as well as Syk phosphorylation. The ethanol treatment increased the phagocytic activity, expression of CD206, and IL-10 production; however, reduced ROS production, fungicidal activity, caspase-1 cleavage, and IL-1ß and IL-6 production. Our data also showed that the presence of ethanol reduced the differentiation of Th1 and Th17 cells and increased the frequency of Th2 cells. Our results indicated that ethanol exposure could suppress effector function of macrophages, possibly leading to the polarization of M2 macrophages. The ethanol modulates the expression of costimulatory and antigen-presentation molecules and interferes with the NLRP3 inflammasome. Altogether, these alterations affect the development of the adaptive response, decreasing the frequency of IL-17, IL-22, and IFN- γ producing cells, and increasing the frequency of IL-4 producing cells. Therefore, exposure to ethanol can impair the capability of macrophages to exert their effector functions and activate the acquired response related to resistance to P. brasiliensis infection.
Asunto(s)
Etanol/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/microbiología , Paracoccidioides/fisiología , Paracoccidioidomicosis/inmunología , Inmunidad Adaptativa/efectos de los fármacos , Antifúngicos/farmacología , Complejo CD3/análisis , Caspasa 1/análisis , Citocinas/análisis , Citocinas/efectos de los fármacos , Citocinas/metabolismo , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Humanos , Inflamasomas/efectos de los fármacos , Inflamasomas/metabolismo , Receptores de Lipopolisacáridos/análisis , Macrófagos/inmunología , Proteína con Dominio Pirina 3 de la Familia NLR/efectos de los fármacos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Peróxidos/metabolismo , Fagocitosis/efectos de los fármacosRESUMEN
BACKGROUND: Pityriasis rosea is a common papulosquamous disorder. However, its etiology and pathogenesis remain unclear. OBJECTIVE: We investigate the types of inflammatory cells infiltrating the lesional skin of pityriasis rosea and demonstrate whether T-cell-mediated immunity is involved in the pathogenesis of this condition or not. METHODS: The biopsies were taken from the lesional skin of 35 cases of patients diagnosed with pityriasis rosea. The specimens were prepared in paraffin sections, then submitted to routine immunohistochemistry procedures using monoclonal antibodies directed against CD3, CD4, CD8, CD20 and CD45RO and horseradish peroxidase-labeled goat anti-human antibodies. The positive sections were determined by the ratio and staining intensity of positive inflammatory cells. RESULTS: The mean score of positive CD3, CD4, CD8, and CD45RO staining was respectively 3.74±3.88, 5.67±4.40, 2.94±3.42 and 7.68±4.33 in these pityriasis rosea patients (P<0.001). The percentage of positive staining was 54.29% (19/35), 69.7% (23/33), 40% (14/35) and 79.41% (27/34) (P<0.05). However, the staining of CD20 was negative in all samples. The mean score of CD3 staining in patients with time for remission ≤60 days (4.90±4.21) was higher than that in patients with time for remission >60 days (2.00±2.5) (P<0.05), whereas no statistical difference in the mean score of CD4, CD8 and CD45RO staining was observed. study liMitations: The sample size and the selected monoclonal antibody are limited, so the results reflect only part of the cellular immunity in the pathogenesis of pityriasis rosea. CONCLUSION: Our findings support a predominantly T-cell mediated immunity in the development of pityriasis rosea.
Asunto(s)
Pitiriasis Rosada/patología , Subgrupos de Linfocitos T/patología , Adolescente , Adulto , Biopsia , Complejo CD3/análisis , Linfocitos T CD4-Positivos/patología , Linfocitos T CD8-positivos/patología , Femenino , Humanos , Inmunidad Celular , Inmunohistoquímica , Antígenos Comunes de Leucocito/análisis , Masculino , Persona de Mediana Edad , Pitiriasis Rosada/inmunología , Valores de Referencia , Coloración y Etiquetado , Subgrupos de Linfocitos T/inmunología , Factores de Tiempo , Adulto JovenRESUMEN
Abstract: Background: Pityriasis rosea is a common papulosquamous disorder. However, its etiology and pathogenesis remain unclear. Objective: We investigate the types of inflammatory cells infiltrating the lesional skin of pityriasis rosea and demonstrate whether T-cell-mediated immunity is involved in the pathogenesis of this condition or not. Methods: The biopsies were taken from the lesional skin of 35 cases of patients diagnosed with pityriasis rosea. The specimens were prepared in paraffin sections, then submitted to routine immunohistochemistry procedures using monoclonal antibodies directed against CD3, CD4, CD8, CD20 and CD45RO and horseradish peroxidase-labeled goat anti-human antibodies. The positive sections were determined by the ratio and staining intensity of positive inflammatory cells. Results: The mean score of positive CD3, CD4, CD8, and CD45RO staining was respectively 3.74±3.88, 5.67±4.40, 2.94±3.42 and 7.68±4.33 in these pityriasis rosea patients (P<0.001). The percentage of positive staining was 54.29% (19/35), 69.7% (23/33), 40% (14/35) and 79.41% (27/34) (P<0.05). However, the staining of CD20 was negative in all samples. The mean score of CD3 staining in patients with time for remission ≤60 days (4.90±4.21) was higher than that in patients with time for remission >60 days (2.00±2.5) (P<0.05), whereas no statistical difference in the mean score of CD4, CD8 and CD45RO staining was observed. study liMitations: The sample size and the selected monoclonal antibody are limited, so the results reflect only part of the cellular immunity in the pathogenesis of pityriasis rosea. Conclusion: Our findings support a predominantly T-cell mediated immunity in the development of pityriasis rosea.
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Adulto Joven , Subgrupos de Linfocitos T/patología , Pitiriasis Rosada/patología , Valores de Referencia , Coloración y Etiquetado , Factores de Tiempo , Biopsia , Inmunohistoquímica , Linfocitos T CD4-Positivos/patología , Subgrupos de Linfocitos T/inmunología , Pitiriasis Rosada/inmunología , Antígenos Comunes de Leucocito/análisis , Complejo CD3/análisis , Linfocitos T CD8-positivos/patología , Inmunidad CelularRESUMEN
INTRODUCTION: This study tested the hypothesis that the inflammatory cell profile (CD3-, CD4-, CD8-, CD20-, and CD68-positive cells) and the expression of immunologic markers (tumor necrosis factor α, interferon-γ, interleukin-6, and interleukin-18) in chronic apical periodontitis are the same between non-HIV-infected patients and HIV-infected patients undergoing highly active antiretroviral therapy (HAART). METHODS: Thirty-four surgically excised chronic apical periodontitis lesions were sampled from 34 patients (17 HIV-infected and 17 non-HIV-infected). The lesions were extracted from teeth with no previous endodontic treatment. All HIV-infected patients were undergoing HAART. The specimens were submitted to histopathologic and immunohistochemical analyses by using an optical microscope. Immunoexpression was graded into 2 levels, focal to weak and moderate to strong. The χ(2), Fisher exact, and Mann-Whitney tests were used to analyze all significant differences between groups. RESULTS: Periapical cysts represented 70.6% and 52.9% of the lesions in the HIV-infected and non-HIV-infected groups, respectively; however, no statistically significant difference was observed (P = .481). There were no statistically significant differences between groups for the inflammatory cell profile and for any of the immunologic markers (P > .05). CONCLUSIONS: There are no statistically significant differences of the cellular profile and expression of immunologic markers in chronic apical periodontitis between non-HIV-infected patients and HIV-infected patients undergoing HAART.
Asunto(s)
Terapia Antirretroviral Altamente Activa/métodos , Biomarcadores , Infecciones por VIH/complicaciones , Periodontitis Periapical/complicaciones , Periodontitis Periapical/inmunología , Periodontitis Periapical/patología , Adulto , Anciano , Antígenos CD/análisis , Antígenos CD20/análisis , Antígenos de Diferenciación Mielomonocítica/análisis , Brasil , Complejo CD3/análisis , Antígenos CD4/análisis , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Humanos , Inmunohistoquímica , Interferón gamma/inmunología , Interleucina-18/inmunología , Interleucina-6/inmunología , Masculino , Persona de Mediana Edad , Granuloma Periapical/inmunología , Granuloma Periapical/patología , Periodontitis Periapical/diagnóstico por imagen , Quiste Radicular/complicaciones , Quiste Radicular/inmunología , Quiste Radicular/patología , Fumar , Linfocitos T/inmunología , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Hydroa vacciniforme-like lymphoma is a recently recognized cutaneous T-cell lymphoma associated with Epstein-Barr virus. The disease is observed in children of Latin American or Asian ethnicity. The authors report the clinical, histopathological, and immunophenotypical features of 9 new Mexican patients (M:F = 2:1; mean age, 14.5 years; median age, 13.3 years; age range, 4-27 years), expanding on previous observations of this elusive disease. The most common clinical aspects were persistent facial edema with necroses and pitted scars. Histopathological analyses revealed variably dense lymphoid infiltrates with common angiodestructive features. Neoplastic cells expressed CD3 and cytotoxic markers in all cases and were constantly positive for Epstein-Barr virus (EBER-1). Expression of other markers was variable. Follow-up data revealed that all patients died within 6 months or less, thus showing a very aggressive course with poor prognosis.
Asunto(s)
Edema/patología , Infecciones por Virus de Epstein-Barr/complicaciones , Cara/patología , Neoplasias Faciales/patología , Hidroa Vacciniforme/patología , Linfoma Cutáneo de Células T/patología , Adolescente , Adulto , Complejo CD3/análisis , Niño , Preescolar , Cicatriz/patología , Cicatriz/virología , Edema/virología , Extremidades/patología , Neoplasias Faciales/química , Neoplasias Faciales/virología , Femenino , Humanos , Hidroa Vacciniforme/virología , Inmunohistoquímica , Linfoma Cutáneo de Células T/química , Linfoma Cutáneo de Células T/virología , Masculino , México , Necrosis/patología , Necrosis/virología , Pronóstico , Torso/patología , Adulto JovenRESUMEN
BACKGROUND: Inflammatory pseudotumor is a little known and uncommon condition. The debate continues whether it represents an inflammatory lesion or is a true neoplasm. It is considered a reactive process usually characterized by irregular growth of inflammatory cells. It has been described at various sites, the most common being the lung. The aim of this report is to emphasize the difficulty in the initial diagnosis. CLINICAL CASE: We present the case of a 56-year-old male who reports an 8-month history of dry cough, dyspnea, fatigue, weakness and weight loss of 20 kg. We performed two biopsies, one positive for malignancy without response to medical treatment and the second reporting chronic granulomatous inflammation. The patient underwent sternotomy, revealing a tumor of 20 × 17 × 10 cm, weighing approximately 2 kg. The tumor was dependent on the anterior mediastinum surrounding large vessels, and venous brachiocephalic, pericardium and both pleuras with firm adhesions to the right lung. Pathological report was as follows: inflammatory myofibroblastic tumor with positive immunohistochemistry for CD20 and CD3. Postoperative course was satisfactory and 1 year after surgery there was no evidence of recurrence. CONCLUSION: Inflammatory pseudotumor is a benign neoplasm of unknown origin with a chronic course. It can simulate a malignant tumor, causing constitutional manifestations, airway obstruction, cardiac alterations or other symptoms according to their location. Diagnosis is based on radiological features and direct biopsy. Treatment of choice is complete resection of the tumor with a favorable long-term outcome.
ANTECEDENTES: el pseudotumor inflamatorio es una afección poco frecuente y conocida de la que aún se debate si es una lesión inflamatoria o se trata de una verdadera neoplasia. Se considera un proceso generalmente reactivo caracterizado por crecimiento irregular de células inflamatorias. Se ha descrito en diversos sitios y la localización más frecuente es el pulmón. El objetivo de este caso es denotar la dificultad diagnóstica inicial. Caso clínico: paciente masculino de 56 años de edad, con ocho meses de evolución del padecimiento, con tos seca, disnea progresiva, astenia, adinamia y pérdida ponderal de 20 kg. Se realizaron dos biopsias; una positiva a malignidad sin respuesta al tratamiento médico y la segunda que reportó inflamación crónica granulomatosa. En la esternotomía se encontró un tumor de 20 × 17 × 10 cm, con peso aproximado de 2 kg, dependiente del mediastino anterior que rodeaba grandes vasos, el tronco braquiocefálico venoso al igual que el pericardio; ambas pleuras con adherencias firmes al pulmón derecho. El reporte histopatológico fue de: tumor miofibroblástico inflamatorio con inmunohistoquímica positiva para CD20 y CD3. La evolución postoperatoria fue satisfactoria y a un año de la cirugía sin evidencia de recurrencia. CONCLUSIÓN: el pseudotumor inflamatorio es una neoplasia benigna de origen indeterminado y de evolución crónica que puede simular un tumor maligno, con manifestaciones constitucionales y de obstrucción aérea, cardiaca o según su localización. El diagnóstico se basa en las características radiológicas y la biopsia directa, el tratamiento de elección consiste en la resección completa del tumor, con resultado favorable a largo plazo.
Asunto(s)
Granuloma de Células Plasmáticas/patología , Enfermedades del Mediastino/patología , Enfermedades Torácicas/patología , Antígenos CD20/análisis , Complejo CD3/análisis , Granuloma de Células Plasmáticas/diagnóstico , Granuloma de Células Plasmáticas/epidemiología , Granuloma de Células Plasmáticas/cirugía , Humanos , Masculino , Enfermedades del Mediastino/diagnóstico , Enfermedades del Mediastino/cirugía , Persona de Mediana Edad , Enfermedades Torácicas/diagnóstico , Enfermedades Torácicas/cirugíaRESUMEN
BACKGROUND: Apoptosis is a highly controlled process of cell death that can be induced by periodontopathogens. The present study aimed to investigate the expression of Fas and Bcl-2 proteins by CD3+ T cells in vitro under stimulation by total Porphyromonas gingivalis antigens and purified recombinant P. gingivalis HmuY protein. RESULTS: CD3+ T cells derived from CP patients and stimulated with HmuY expressed higher levels of Bcl-2 compared to identical cells stimulated with P. gingivalis crude extract or cells derived from NP control subjects (p = 0.043). CONCLUSION: The authors hypothesize that P. gingivalis HmuY plays a role in the pathogenesis of chronic periodontitis, possibly by reducing or delaying apoptosis in T cells through a pathway involving the Bcl-2 protein.
Asunto(s)
Proteínas Bacterianas/metabolismo , Complejo CD3/análisis , Interacciones Huésped-Patógeno , Porphyromonas gingivalis/fisiología , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Linfocitos T/microbiología , Receptor fas/biosíntesis , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodontitis/microbiología , Porphyromonas gingivalis/aislamiento & purificación , Proteínas Proto-Oncogénicas c-bcl-2/genética , Linfocitos T/química , Adulto Joven , Receptor fas/genéticaRESUMEN
Pediatric normal brachial biceps (14 specimens) and quadriceps muscles (14 specimens) were studied by immunohistochemistry to quantify fiber-type, diameter and distribution, capillary density, presence of inflammatory cells (CD3, CD20, CD68) and expression of neonatal myosin and MHC class 1 proteins. Brachial biceps showed more fast-twitch fibers and lower capillary/fiber ratio than quadriceps. The mean diameter of both fiber types was smaller in biceps than quadriceps. Fast-fibers were smaller than slow-fibers, and capillary/fiber ratio was < 1.0 in both muscles. Fiber size and capillary / fiber ratio increased with age. Normal limits for infiltrating haematopoietic cells were <4 T lymphocytes, or CD68+ cells, very few B cells, < 6 neonatal myosin positive fibers, and no fibers MHC class 1 positive in one x20 field, for both muscles. The present comparison of quantitative findings between brachial biceps and quadriceps may allow standardization of the assessment of pathological changes in both pediatric muscles.
Asunto(s)
Músculo Esquelético/anatomía & histología , Músculo Cuádriceps/anatomía & histología , Factores de Edad , Antígenos CD/análisis , Antígenos CD20/análisis , Antígenos de Diferenciación Mielomonocítica/análisis , Biomarcadores/análisis , Biopsia , Complejo CD3/análisis , Niño , Preescolar , Femenino , Antígenos de Histocompatibilidad Clase I/análisis , Humanos , Inmunohistoquímica , Masculino , Fibras Musculares de Contracción Rápida/química , Fibras Musculares de Contracción Lenta/química , Músculo Esquelético/química , Miosinas/análisis , Tamaño de los Órganos , Músculo Cuádriceps/química , Valores de ReferenciaRESUMEN
OBJECTIVE: The aim of this study was to describe the clinicopathological and immunohistochemical features of 19 cases of oral eosinophilic ulcers and discuss the hypothesis that this entity could represent a spectrum of the CD30(+) lymphoproliferative disorder. MATERIAL AND METHODS: Clinical data concerning gender, age, affected site, and clinical presentation of 19 patients were collected and a broad immunohistochemical panel was carried out. Eosinophil distribution in relation to muscular tissue was evaluated using an Aperio ScanScope CS scanner. RESULTS: The mean age of the patients was 58.6 years, with a male preponderance. A single painful ulcer in the tongue was the most common clinical presentation. There was no predilection of eosinophils for surrounding muscular fibers because this population was equally distributed in areas adjacent to and distant from these structures. The inflammatory infiltrate was mainly formed by cytotoxic T lymphocytes and CD30 expression was not limited to large atypical cells; it also stained small reactive lymphocytes. CONCLUSIONS: Considering the clinical, histopathological, and immunohistochemical characteristics, oral eosinophilic ulcers must be considered a self-limiting reactive condition.
Asunto(s)
Eosinofilia/patología , Úlceras Bucales/patología , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD20/análisis , Complejo CD3/análisis , Antígenos CD8/análisis , Diagnóstico Diferencial , Eosinófilos/patología , Femenino , Granuloma Piogénico/diagnóstico , Granzimas/análisis , Humanos , Hiperplasia , Antígeno Ki-1/análisis , Linfocitos/patología , Trastornos Linfoproliferativos/diagnóstico , Masculino , Mastocitos/patología , Persona de Mediana Edad , Fibras Musculares Esqueléticas/patología , Necrosis , Peroxidasa/análisis , Estudios Retrospectivos , Linfocitos T Citotóxicos/patología , Enfermedades de la Lengua/patología , Neoplasias de la Lengua/diagnóstico , Tuberculosis Bucal/diagnósticoRESUMEN
OBJECTIVE: The overall objective of this study was to assess the oral manifestations and their association with immunologic status and health history, of individuals with hypogammaglobulinemia. STUDY DESIGN: A case-controlled study of 100 subjects with hypogammaglobulinemia and 93 control individuals was performed. All participants were examined for dental caries, periodontal disease, mucosal lesions/infections, and general oral health problems. Decayed, missing, filled teeth and community periodontal index were recorded. Complete blood count, serum immunoglobulins, and lymphocyte immunophenotyping were measured on the same day of the oral health assessment. RESULTS: Individuals with hypogammaglobulinemia showed higher prevalence of enamel hypoplasia and complaints of dry mouth, and lower prevalence of dental caries and periodontal disease. CONCLUSIONS: The systemic conditions associated with hypogammaglobulinemia were not associated with enhanced susceptibility to caries, gingivitis, or periodontitis; however, individuals with hypogammaglobulinemia were more likely to report more episodes of recurrent aphthous ulcers compared with control individuals.
Asunto(s)
Agammaglobulinemia/complicaciones , Enfermedades de la Boca/etiología , Adolescente , Adulto , Anciano , Linfocitos B/patología , Recuento de Células Sanguíneas , Complejo CD3/análisis , Linfocitos T CD4-Positivos/patología , Linfocitos T CD8-positivos/patología , Estudios de Casos y Controles , Índice CPO , Caries Dental/etiología , Hipoplasia del Esmalte Dental/etiología , Femenino , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Células Asesinas Naturales/patología , Masculino , Persona de Mediana Edad , Enfermedades Periodontales/etiología , Índice Periodontal , Estomatitis Aftosa/etiología , Estomatitis Herpética/etiología , Linfocitos T/clasificación , Xerostomía/etiología , Adulto JovenRESUMEN
UNLABELLED: Mycosis fungoides (MF), the most common form of cutaneous T cell lymphoma (CTCL), is mainly manifested in the elderly. However, it has been described in children and teenagers. OBJECTIVES: To report six patients with mycosis fungoides diagnosed in patients under 20 years of age. Our focus is on epidemiologic data, clinical features, histopathological aspects, and immunophenotypical findings. METHODS: The files of all patients diagnosed with CTCL at Hospital Universitário Antônio Pedro (HUAP) / Universidade Federal Fluminense (UFF), Niterói, Brazil, from 2007 to 2010 were searched to identify patients under 20 years of age. Slides were reviewed with routine methods (H&E) and immunohistochemical stains by two dermatopathologists and one surgical pathologist. RESULTS: Among a total of 66 patients with MF, six were children and adolescents between five and nineteen years of age. Most of them had dark skin and presented with the hypopigmented variant of MF; some expressed the T cell CD8+ phenotype, although the prognosis remains the same as for classical CTCL. The main histopathological findings were basilar lymphocytes, Pautrier microabscesses, eccrine infiltration, and dermal fibrosis. One patient had shown pityriasis lichenoides chronica for 10 years before the diagnosis of MF. CONCLUSIONS: The incidence of juvenile mycosis fungoides has increased, corresponding to 9.1 percent of patients diagnosed with MF in our institution in four years. In this sample, 83.3 percent of the patients had the hypopigmented variant and 50 percent of them showed the CD3+/CD8+ T cells phenotype. We emphasize the occurrence of pityriasis lichenoides chronica before the onset of MF in one of our cases. This association, although rare, must be considered in cases of atypical evolution of PLC. The diagnosis of hypopigmented MF should also be considered in patients when hypochromic patches are persistent. We would like to highlight the importance of Pautrier microabscesses, basilar distribution, and eccrine involvement by neoplastic lymphocytes as histopathological diagnostic criteria for this variant of MF.
Asunto(s)
Hipopigmentación/patología , Micosis Fungoide/patología , Neoplasias Cutáneas/patología , Adolescente , Brasil , Complejo CD3/análisis , Antígenos CD8/análisis , Niño , Preescolar , Humanos , Hipopigmentación/inmunología , Masculino , Micosis Fungoide/inmunología , Neoplasias Cutáneas/inmunología , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVE: Human chronic periodontitis is an inflammatory process characterized by dense accumulation of immune cells in the periodontal tissue. The periodontitis can lead to loss of teeth in the patient and the pathogenesis of this disease is not completely known. This study tested the hypothesis that chronic periodontitis-affected sites can harbor betaherpesviruses and that viruses are linked to a profile of the inflammatory infiltrate. MATERIAL AND METHODS: Biopsies of periodontal tissue were taken from periodontitis-affected patients and from healthy subjects. Immunohistochemistry was performed to count CD19(+) B cells, CD3(+) total T cells, T-CD4(+) and T-CD8(+) cell subsets, and PCR was performed to detect cytomegalovirus and human herpesvirus 6 and 7 in the samples. One slide of each sample was stained with Giemsa for histopathological examination and to evaluate the quality of the cellular infiltrate. RESULTS: As expected, tissues collected from healthy subjects presented no significant level of inflammatory infiltration and were therefore excluded from immunostaining procedures. Results showed that CD19(+) B cells were in higher number than CD3(+) T cells in the periodontitis-affected tissue, but this was not statistically significant. The T-CD4(+) lymphocyte subset was significantly higher than the T-CD8(+) lymphocyte subset (p = 0.004) in the samples. Cytomegalovirus and human herpesvirus 7 were found at periodontitis-affected sites, but not in tissue collected from healthy subjects (p = 0.04 and p = 0.04, respectively). Human herpesvirus 6 was rarely detected. We found a correlation between cytomegalovirus and lower CD19(+) /CD3(+) ratios (ratio < 0.9, p = 0.003) and between human herpesvirus 7 and lower CD19(+) /CD3(+) ratios (ratio < 0.9, p = 0.003) and higher CD4(+) /CD8(+) ratios (ratio > 1.1, p = 0.002). CONCLUSION: This study shows that cytomegalovirus and human herpesvirus 7 can be present at periodontitis-affected sites but are uncommon at healthy periodontal sites. Moreover, our data suggest that cytomegalovirus can be related to an inflammatory infiltrate with predominance of CD3(+) T cells, whereas human herpesvirus 7 can be associated with an infiltrate with predominance of T-CD4(+) cells. However, further studies are necessary to support this hypothesis. Herpesviruses could play a role in human chronic periodontitis by modulation of the T cell response.
Asunto(s)
Linfocitos T CD4-Positivos/patología , Periodontitis Crónica/inmunología , Citomegalovirus/aislamiento & purificación , Herpesvirus Humano 7/aislamiento & purificación , Linfocitos T/patología , Adulto , Anciano , Antígenos CD19/análisis , Linfocitos B/inmunología , Linfocitos B/patología , Complejo CD3/análisis , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/patología , Periodontitis Crónica/virología , Citomegalovirus/inmunología , Femenino , Herpesvirus Humano 6/inmunología , Herpesvirus Humano 6/aislamiento & purificación , Herpesvirus Humano 7/inmunología , Humanos , Inmunofenotipificación , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Linfocitos T/inmunología , Adulto JovenRESUMEN
Narcolepsy has been studied as a possible autoimmune disease for many years, and recent findings lend more credence to this belief. Although recent and important advances have been done, no study has analyzed the role of the CD40L in patients with narcolepsy. The purpose of this study was to assess CD40L levels, CD3, TCD4, TCD8, CD19, and CD56 lymphocytes, as well as levels of tumor necrosis factor-α and interleukin-6 in narcoleptic patients. We quantified the levels of CD40L, different types of lymphocytes, and levels of tumor necrosis factor-α and interleukin-6 in narcoleptic patients and control subjects. Narcoleptic patients had lower levels of CD40L. Total lymphocytes; CD3, and TCD4 were lower than in the control group. Our findings highlight the important role of CD40L in narcolepsy.
Asunto(s)
Ligando de CD40/inmunología , Cadenas beta de HLA-DQ/análisis , Linfopenia/inmunología , Narcolepsia/inmunología , Adulto , Brasil , Complejo CD3/análisis , Complejo CD3/inmunología , Antígenos CD4/análisis , Antígenos CD4/inmunología , Ligando de CD40/análisis , Estudios de Casos y Controles , Femenino , Cadenas beta de HLA-DQ/genética , Cadenas beta de HLA-DQ/inmunología , Humanos , Interleucina-6/sangre , Interleucina-6/inmunología , Péptidos y Proteínas de Señalización Intracelular/líquido cefalorraquídeo , Recuento de Linfocitos , Linfocitos/citología , Linfocitos/inmunología , Linfopenia/sangre , Linfopenia/complicaciones , Masculino , Persona de Mediana Edad , Narcolepsia/sangre , Narcolepsia/complicaciones , Neuropéptidos/líquido cefalorraquídeo , Orexinas , Reacción en Cadena de la Polimerasa , Polisomnografía , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic joint inflammation and continuous immune cell infiltration in the synovium. These changes are linked to inflammatory cytokine release, leading to eventual destruction of cartilage and bone. During the last decade new therapeutic modalities have improved the prognosis, with the introduction of novel biological response modifiers including anti-TNFalpha CTLA4Ig and, more recently, anti-IL6. In the present study we looked at the immunological effects of these three forms of therapy. Serum, obtained from patients with RA was analyzed for TNFalpha, IL6, IL10, IFNgamma, and VEGF, and in parallel, circulating plasmacytoid and myeloid dendritic cells (DC) were enumerated before and after three infusions of the respective biological treatments. After treatment with anti-IL6, we found a significant reduction of IL6 and TNFalpha levels and the percentage of both DC subsets decreased. Although the results did not reach statistical significance for anti-TNFalpha treatment, similar trends were observed. Meanwhile, CTLA4Ig therapy led to the reduction IFNgamma levels only. None of the treatments modified significantly VEGF or IL10 levels. These findings may explain why patients with RA improve more rapidly on IL-6 therapy than with the other two modalities.
Asunto(s)
Artritis Reumatoide/terapia , Terapia Biológica/métodos , Citocinas/sangre , Células Dendríticas/efectos de los fármacos , Abatacept , Adulto , Anticuerpos/inmunología , Anticuerpos/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/sangre , Artritis Reumatoide/inmunología , Complejo CD3/análisis , Células Dendríticas/citología , Células Dendríticas/inmunología , Femenino , Citometría de Flujo , Humanos , Inmunoconjugados/uso terapéutico , Interferón gamma/sangre , Interleucina-10/sangre , Subunidad alfa del Receptor de Interleucina-3/análisis , Interleucina-6/sangre , Interleucina-6/inmunología , Receptores de Lipopolisacáridos/análisis , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/inmunología , Factor A de Crecimiento Endotelial Vascular/sangreRESUMEN
The lymphoid follicles (LF) found in the false vocal cords (FVC) protect the upper air tracts, similar to the lymphoid tissue associated to the respiratory mucosas. However, studies that characterize the phenotype of cells like larynx-associated lymphoid tissue (LALT) are lacking. We analyzed the FVC of autopsied adults according to morphometric and immunohistochemical criteria and defined their possible role as LALT. We analyzed 249 FVC. Primary antibodies, CD68+ macrophages, CD20+, CD3+, and FDC+ were used for the evaluation of inflammatory cell phenotypes. In 40.6% of the cases, there was an inflammatory reaction. In 42.2% of the cases, LF were identified in the submucosa. In 17.3% of the cases, neither LF nor mononuclear cells were identified in the FVC, and these patients were from an older age group (p=0.013). A significant increase in the number of all LF cell phenotypes was observed in patients with pulmonary inflammation; the difference in both T- and B-lymphocytes was statistically significant (p=0.010). The morphological findings of LF suggest a probable participation of the FVC in the protection of the larynx and lungs, and similarity to LALT.
Asunto(s)
Laringe/patología , Tejido Linfoide/patología , Pliegues Vocales/patología , Adulto , Anciano , Antígenos CD/análisis , Antígenos CD20/análisis , Antígenos de Diferenciación Mielomonocítica/análisis , Autopsia , Linfocitos B/inmunología , Linfocitos B/patología , Complejo CD3/análisis , Células Dendríticas Foliculares/inmunología , Células Dendríticas Foliculares/patología , Humanos , Inmunofenotipificación , Inflamación/inmunología , Inflamación/patología , Laringe/inmunología , Tejido Linfoide/inmunología , Macrófagos/inmunología , Macrófagos/patología , Persona de Mediana Edad , Fenotipo , Estudios Retrospectivos , Linfocitos T/inmunología , Linfocitos T/patología , Pliegues Vocales/inmunologíaRESUMEN
Some cases of T-cell acute lymphoblastic leukaemia (ALL) express markers found in natural-killer (NK) cells, such as CD56 and CD16. Out of 84 T-cell ALL cases diagnosed at our Institution, CD56 and/or CD16 was detected in 24 (28.5%), which we designated T/NK-ALL group. Clinical features, laboratory characteristics, survival and expression of cytotoxic molecules were compared in T/NK-ALL and T-ALL patients. Significant differences were observed regarding age (24.9 vs. 16.4 years in T/NK-ALL and T-ALL, respectively, P = 0.006) and platelet counts (177 x 10(9)/l vs. 75 x 10(9)/l in T/NK-ALL and T-ALL, respectively, P = 0.03). Immunophenotypic analysis demonstrated that CD34, CD45RA and CD33 were more expressed in T/NK-ALL patients, whereas CD8 and terminal deoxynucleotidyl transferase were more expressed in T-ALL patients (P < 0.05). The mean overall survival (863 vs. 1869 d, P = 0.02) and disease-free survival (855 vs. 2095 d, P = 0.002) were shorter in patients expressing CD56/CD16. However, multivariate analysis identified CD56/CD16 as an independent prognostic factor only for DFS. Cytotoxic molecules were highly expressed in T/NK-ALL compared to T-ALL. Perforin, granzyme B and TIA-1 were detected in 12/17, 4/17 and 7/24 T/NK-ALL patients and in 1/20, 0/20 and 1/20 T-ALL respectively (P < 0.001, P = 0.036 and P = 0.054). Therefore, the presence of CD56/CD16 was associated with distinct clinical features and expression of cytotoxic molecules in the blasts.
Asunto(s)
Antígeno CD56/análisis , Células Asesinas Naturales/inmunología , Leucemia-Linfoma Linfoblástico de Células T Precursoras/inmunología , Receptores de IgG/análisis , Adolescente , Adulto , Factores de Edad , Antígenos CD/análisis , Antígenos CD34/análisis , Antígenos de Diferenciación Mielomonocítica/análisis , Biomarcadores/análisis , Complejo CD3/análisis , Supervivencia sin Enfermedad , Femenino , Citometría de Flujo , Granzimas/análisis , Humanos , Inmunofenotipificación , Estimación de Kaplan-Meier , Antígenos Comunes de Leucocito/análisis , Masculino , Perforina/análisis , Recuento de Plaquetas , Proteínas de Unión a Poli(A)/análisis , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidad , Lectina 3 Similar a Ig de Unión al Ácido Siálico , Tasa de Supervivencia , Antígeno Intracelular 1 de las Células T , Resultado del Tratamiento , Adulto JovenRESUMEN
Angiogenic T/natural killer (NK)-cell lymphoma is a non-Hodgkin lymphoma characterized by necrosis and vascular destruction that is strongly associated with Epstein-Barr virus and AIDS. Early diagnosis is essential to improve the chances of patient survival, but severe local inflammatory infiltrate impairs histologic diagnosis by obscuring neoplastic cells. The most common markers are CD2, CD56, cytoplasmic CD3, and CD43 EBV. We describe 3 cases of angiogenic T/NK-cell lymphoma that show the diverse presentation of the same disease. Patient 1 was HIV positive and had nasal obstruction, facial edema, and ulceration of the nasal mucosa. Patient 2 had fever, a sore throat, and weight loss. Patient 3 had facial edema, fever, proptosis, and rapid development of neurologic alterations. Several biopsies were needed for histologic confirmation in these patients, despite positivity for the CD3 and CD56 markers.
Asunto(s)
Linfoma no Hodgkin/patología , Complejo CD3/análisis , Antígeno CD56/análisis , Humanos , Células Asesinas Naturales/patología , Linfoma de Células T/patologíaRESUMEN
BACKGROUND: The meaning and clinical implications of the Quilty effect (QE) are not entirely clear. In some biopsies we have found complement split C4d deposition in QE areas, but we do fully comprehend the frequency or pathogenic relationships involved. The objective of this study was to gain insight into the immunologic events involved in the QE, and to understand if and how it relates to complement activation. METHODS: Protocol allograft biopsies (January to December 2005) with evidence of the QE, without cellular rejection or changes suspicious for antibody-mediated rejection, were selected for C4d, CD3, CD20 and CD68 immunohistochemistry. RESULTS: Among 128 allograft biopsies (42 patients), 17 (11 patients) fulfilled the inclusion criteria. Eleven of the 17 biopsies (64.7%), from 8 patients, showed C4d deposition in the endocardium; the positivity was interestingly linear in the endocardium and surrounded by the lymphocytes forming the Quilty lesion. In some cases, the linear C4d deposition extended to the endocardium surrounding the QE area. This pattern was not detected in any of 66 heart allograft biopsies without the QE. B cells were second to T cells in their contribution to the QE, comprising a median of 40% (range, 20% to 50%) of the cells. C4d deposition was not associated with clinical alterations. CONCLUSIONS: The QE is frequently associated with C4d deposition in the endocardium of patients without evidence of rejection. This event suggests a pathogenic relationship between the QE and complement activation. It is possible that the simultaneous presence of both features in an allograft heart biopsy, without evidence of rejection, indicates better adaptation of allograft to host ("accommodation"); however, the precise meaning and implications are not yet known.
Asunto(s)
Complemento C4b/análisis , Endocardio/inmunología , Rechazo de Injerto/inmunología , Trasplante de Corazón/inmunología , Miocardio/inmunología , Fragmentos de Péptidos/análisis , Antígenos CD , Antígenos CD20 , Antígenos de Diferenciación Mielomonocítica , Complejo CD3/análisis , Endocardio/patología , Femenino , Rechazo de Injerto/patología , Trasplante de Corazón/patología , Humanos , Inmunoquímica , Masculino , Miocardio/patología , Estudios Retrospectivos , Trasplante HomólogoRESUMEN
Phenotypic features of peripheral blood leukocytes have been investigated as a pre-requisite to characterize the protective immunity attributed to both Leishvaccine and Leishmune. Our results showed that either those vaccine were accompanied by distinct profiles on innate immune compartment. While Leishvaccine promoted early changes in phenotypic features of neutrophils and eosinophils with late involvement of monocytes, Leishmune induced early and persistent activation of neutrophils and monocytes, without changes on eosinophil activation status. Regarding the adaptive immunity, Leishvaccine sponsored a mixed profile, associated with phenotypic changes of T and B-lymphocytes. Major phenotypic changes in CD4+ T-cells with transient activation of CD8+ T-cell, besides decreased frequency of B-cell expressing CD32 were the hallmark of Leishvaccine. In contrast, Leishmune was associated with phenotypic changes in T-lymphocytes, particularly in CD8+ T-cells, and selective up-regulation of CD3+CD5+LowCD8+ cells. We hypothesized that this dissimilar alteration in immunological events would represent phenomenon directly related with the molecular nature of these vaccines besides the distinct adjuvants employed. However, it is important to emphasize that both immunobiologicals are able to activate phagocytes and CD8+ T-cells and therefore could be considered priority vaccines with a high-quality immunogenic potential against CVL.