RESUMO
This study analyzed the type 1 and type 2T helper (Th1/Th2) cytokines (including interleukins), immune cellular, matrix profile, and pathogens in granulomas with unexplained etiology compared to those with infectious and noninfectious etiology. Surgical lung biopsies from 108 patients were retrospectively reviewed. Histochemistry, immunohistochemistry, immunofluorescence, morphometry and polymerase chain reaction were used, respectively, to evaluate total collagen and elastin fibers, collagen I and III, immune cells, cytokines, matrix metalloproteinase-9, myofibroblasts, and multiple usual and unusual pathogens. No relevant polymerase chain reaction expression was found in unexplained granulomas. A significant difference was found between the absolute number of eosinophils, macrophages, and lymphocytes within granulomas compared to uninvolved lung tissue. Granulomas with unexplained etiology (UEG) presented increased number of eosinophils and high expression of interleukins (ILs) IL-4/IL-5 and transforming growth factor-ß. In sarcoidosis, CD4/CD8 cell number was significantly higher within and outside granulomas, respectively; the opposite was detected in hypersensitivity pneumonitis. Again, a significant difference was found between the high number of myofibroblasts and matrix metalloproteinase-9 in UEG, hypersensitivity pneumonitis, and sarcoidosis compared to granulomas of tuberculosis. Granulomas of paracoccidioisis exhibited increased type I collagen and elastic fibers. Th1 immune cellular profile was similar among granulomas with unexplained, infectious, and noninfectious etiology. In contrast, modulation of Th2 and matrix remodeling was associated with more fibroelastogenesis and scarring of lung tissue in UEG compared to infectious and noninfectious. We concluded that IL-4/IL-5 and transforming growth factor-ß might be used as surrogate markers of early fibrosis, reducing the need for genotyping, and promise therapeutic target in unexplained granulomas.
Assuntos
Granuloma do Sistema Respiratório/imunologia , Granuloma do Sistema Respiratório/patologia , Pneumopatias/imunologia , Pneumopatias/patologia , Adulto , Matriz Extracelular/patologia , Feminino , Granuloma do Sistema Respiratório/microbiologia , Humanos , Pneumopatias/microbiologia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: To investigate the significance of cellular immune markers, as well as that of collagen and elastic components of the extracellular matrix, within granulomatous structures in biopsies of patients with pulmonary or extrapulmonary sarcoidosis. METHODS: We carried out qualitative and quantitative evaluations of inflammatory cells, collagen fibers, and elastic fibers in granulomatous structures in surgical biopsies of 40 patients with pulmonary and extrapulmonary sarcoidosis using histomorphometry, immunohistochemistry, picrosirius red staining, and Weigert's resorcin-fuchsin staining. RESULTS: The extrapulmonary tissue biopsies presented significantly higher densities of lymphocytes, macrophages, and neutrophils than did the lung tissue biopsies. Pulmonary granulomas showed a significantly higher number of collagen fibers and a lower density of elastic fibers than did extrapulmonary granulomas. The amount of macrophages in the lung samples correlated with FVC (p < 0.05), whereas the amount of CD3+, CD4+, and CD8+ lymphocytes correlated with the FEV1/FVC ratio and VC. There were inverse correlations between TLC and the CD1a+ cell count (p < 0.05), as well as between DLCO and collagen/elastic fiber density (r = -0.90; p = 0.04). CONCLUSIONS: Immunophenotyping and remodeling both showed differences between pulmonary and extrapulmonary sarcoidosis in terms of the characteristics of the biopsy samples. These differences correlated with the clinical and spirometric data obtained for the patients, suggesting that two different pathways are involved in the mechanism of antigen clearance, which was more effective in the lungs and lymph nodes.
Assuntos
Matriz Extracelular/imunologia , Imunidade Celular , Imunofenotipagem/métodos , Sarcoidose/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Biópsia , Colágeno/imunologia , Tecido Elástico/imunologia , Tecido Elástico/patologia , Matriz Extracelular/patologia , Feminino , Granuloma do Sistema Respiratório/imunologia , Granuloma do Sistema Respiratório/patologia , Humanos , Pulmão/imunologia , Pulmão/patologia , Linfonodos/imunologia , Linfonodos/patologia , Linfócitos/imunologia , Macrófagos Alveolares/imunologia , Masculino , Pessoa de Meia-Idade , Sarcoidose/patologia , Sarcoidose Pulmonar/imunologia , Sarcoidose Pulmonar/patologiaRESUMO
OBJETIVO: Investigar o significado de marcadores de imunidade celular e de componentes elásticos/colágeno da matriz extracelular em estruturas granulomatosas em biópsias de pacientes com sarcoidose pulmonar ou extrapulmonar. MÉTODOS: Determinações qualitativas e quantitativas de células inflamatórias, de fibras de colágeno e de fibras elásticas em estruturas granulomatosas em biópsias cirúrgicas de 40 pacientes com sarcoidose pulmonar e extrapulmonar foram realizadas por histomorfometria, imuno-histoquímica, e técnicas de coloração com picrosirius e resorcina-fucsina de Weigert. RESULTADOS: A densidade de linfócitos, macrófagos e neutrófilos nas biópsias extrapulmonares foi significativamente maior do que nas biópsias pulmonares. Os granulomas pulmonares apresentaram uma quantidade significativamente maior de fibras de colágeno e menor densidade de fibras elásticas que os granulomas extrapulmonares. A quantidade de macrófagos nos granulomas pulmonares correlacionou-se com CVF (p < 0,05), ao passo que as quantidades de linfócitos CD3+, CD4+ e CD8+ correlacionaram-se com a relação VEF1/CVF e com CV. Houve correlações negativas entre CPT e contagem de células CD1a+ (p < 0,05) e entre DLCO e densidade de fibras colágenas/elásticas (r = -0,90; p = 0,04). CONCLUSÕES: A imunofenotipagem e o remodelamento apresentaram características diferentes nas biópsias dos pacientes com sarcoidose pulmonar e extrapulmonar. Essas diferenças correlacionaram-se com os dados clínicos e espirométricos dos pacientes, sugerindo que há duas vias envolvidas no mecanismo de depuração de antígenos, que foi mais eficaz nos pulmões e linfonodos.
OBJECTIVE: To investigate the significance of cellular immune markers, as well as that of collagen and elastic components of the extracellular matrix, within granulomatous structures in biopsies of patients with pulmonary or extrapulmonary sarcoidosis. METHODS: We carried out qualitative and quantitative evaluations of inflammatory cells, collagen fibers, and elastic fibers in granulomatous structures in surgical biopsies of 40 patients with pulmonary and extrapulmonary sarcoidosis using histomorphometry, immunohistochemistry, picrosirius red staining, and Weigert's resorcin-fuchsin staining. RESULTS: The extrapulmonary tissue biopsies presented significantly higher densities of lymphocytes, macrophages, and neutrophils than did the lung tissue biopsies. Pulmonary granulomas showed a significantly higher number of collagen fibers and a lower density of elastic fibers than did extrapulmonary granulomas. The amount of macrophages in the lung samples correlated with FVC (p < 0.05), whereas the amount of CD3+, CD4+, and CD8+ lymphocytes correlated with the FEV1/FVC ratio and VC. There were inverse correlations between TLC and the CD1a+ cell count (p < 0.05), as well as between DLCO and collagen/elastic fiber density (r = -0.90; p = 0.04). CONCLUSIONS: Immunophenotyping and remodeling both showed differences between pulmonary and extrapulmonary sarcoidosis in terms of the characteristics of the biopsy samples. These differences correlated with the clinical and spirometric data obtained for the patients, suggesting that two different pathways are involved in the mechanism of antigen clearance, which was more effective in the lungs and lymph nodes.
Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Matriz Extracelular/imunologia , Imunidade Celular , Imunofenotipagem/métodos , Sarcoidose/imunologia , Análise de Variância , Biópsia , Colágeno/imunologia , Tecido Elástico/imunologia , Tecido Elástico/patologia , Matriz Extracelular/patologia , Granuloma do Sistema Respiratório/imunologia , Granuloma do Sistema Respiratório/patologia , Pulmão/imunologia , Pulmão/patologia , Linfonodos/imunologia , Linfonodos/patologia , Linfócitos/imunologia , Macrófagos Alveolares/imunologia , Sarcoidose Pulmonar/imunologia , Sarcoidose Pulmonar/patologia , Sarcoidose/patologiaRESUMO
Tuberculosis/HIV-1 co-infection is responsible for thousands of deaths each year, and previous studies have reported that co-infected individuals display major morphological alterations in tissue granulomas. The purpose of this study was to evaluate immunohistopathological characteristics in lung tissues from pulmonary TB/HIV-1-co-infected individuals. Following autopsy, tuberculosis-positive HIV-1-negative cases displayed granulomas with normal architecture, mainly composed of a mononuclear infiltrate with typical epithelioid, as well as giant cells, and exhibiting caseous necrosis. In contrast, lesions from the TB/HIV-1-co-infected group showed extensive necrosis, poorly formed granulomas, and a marked presence of polymorphonuclear cells. More importantly, TNF staining was greatly reduced in the TB/HIV-1-co-infected individuals. Our data suggest that HIV-1 infection alters the organization of pulmonary granulomas by modulating TNF and, possibly, cell trafficking, leading to an impaired anti-tuberculosis response.
Assuntos
Granuloma do Sistema Respiratório/imunologia , Infecções por HIV/complicações , Pulmão/imunologia , Tuberculose Pulmonar/complicações , Fator de Necrose Tumoral alfa/biossíntese , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Infecções Oportunistas Relacionadas com a AIDS/patologia , Granuloma do Sistema Respiratório/microbiologia , Granuloma do Sistema Respiratório/patologia , Infecções por HIV/imunologia , Infecções por HIV/patologia , HIV-1 , Humanos , Pulmão/microbiologia , Pulmão/patologia , Mycobacterium tuberculosis , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/patologiaRESUMO
A number of clinicopathological manifestations may define the presence of hypersensitivity pneumonitis. Histological study is used to establish the diagnosis and to differentiate the disease from other respiratory disorders. This case report suggests that immunohistological demonstration of the causative antigen in the lung may be a useful diagnostic approach in cases of pigeon hypersensitivity pneumonitis. A 52 year-old woman was studied. She had a prior history of pigeon exposure, and lived in an area with a high prevalence of tuberculosis. Her clinical presentation, respiratory function tests and imaging studies revealed a predominant interstitial lung disease. The results of antiavian antibodies, bronchoalveolar analysis, and other laboratory parameters were non-diagnostic. A lung biopsy showed a prominent granulomatous reaction with a sarcoid-like appearance in some areas, and an interstitial infiltration constituted by lymphocytes, plasma cells and foamy macrophages. Although the disease manifestations were compatible with hypersensitivity pneumonitis, we decided to study the causal antigen by immunohistochemistry. The use of a polyclonal antibody raised against pigeon serum showed a predominant cytoplasmic immunostaining in multinucleated giant cells and histiocytes from lung granulomas. Other respiratory disorders were reasonably excluded. Previous exposure to a known antigen may support the diagnosis of hypersensitivity pneumonitis. Although the inhalation of organic dusts may be clinically evident, the aetiology is commonly evaluated by different challenge tests or immunological methods. We propose that the study of pigeon antigen by immunohistochemistry may be used as part of the diagnostic approach for hypersensitivity pneumonitis.