Imunofenotipagem e remodelamento da matriz extracelular na sarcoidose pulmonar e extrapulmonar / Immunophenotyping and extracellular matrix remodeling in pulmonary and extrapulmonary sarcoidosis

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.

Sarcoidosis in north indian population: A retrospective study.

Background. Sarcoidosis is a systemic granulomatous disease of unknown origin most commonly involving the lungs. Sarcoidosis is frequently misdiagnosed due to its clinico-radiological resemblance to tuberculosis (TB). Hence, the present study was undertaken with the aim of studying the clinico-radiological profile of sarcoidosis in the Indian context. Methods. We retrospectively studied 146 patients diagnosed to have sarcoidosis during the period 2001-2010 at one of the respiratory units at Vallabhbhai Patel Chest Institute. Results. Majority of them (70%) were more than 40 years of age; females comprised 58.2% of the patients. Before coming to our clinic, 30% patients had been misdiagnosed to have TB. Cough (89.7%) was the most common presenting symptom; joint symptoms (28.8%) and end inspiratory crepitations at lung bases (49.3%) were other salient manifestations. Cutaneous involvement and digital clubbing were rarely seen. Pulmonary function testing showed restriction with impaired diffusion in 72.7% patients. The most common radiological feature was bilaterally symmetrical hilar lymphadenopathy. Transbronchial lung biopsy (TBLB) had a very high diagnostic yield (90.8%). Conclusions. Sarcoidosis is often misdiagnosed as TB in India. Transbronchial lung biopsy has high diagnostic yield in sarcoidosis.

Immune responses to mycobacterial antigens in sarcoidosis: A systematic review.

From the time sarcoidosis has been described, there has always been a viewpoint that the disease is in some way related to tuberculosis (TB). Sarcoidosis is a granulomatous disease, which is likely a result of continued presentation of a poorly degradable antigen. Mycobacterium tuberculosis has been a very strong contender for this antigen. Besides the molecular studies demonstrating mycobacterial deoxyribonucleic acid (DNA) in the sarcoid tissue, assessment of immune responses against mycobacterial antigens provides a useful tool to study the role of mycobacteria in the pathogenesis of sarcoidosis. We reviewed the studies focussing on T-cell and B-cell responses to tubercular antigens in patients with sarcoidosis. Pooled data from various studies does provide a suggestive, though not unequivocal evidence in favour of mycobacteria as a cause of sarcoidosis. These findings not only reinforce the possible pathogenic role of mycobacterial antigens in sarcoidosis, but at the same time also limit the clinical utility of molecular and serological studies based on mycobacterial antigens in the differential diagnosis of TB from sarcoidosis, particularly in a country with high endemicity for TB.

Sarcoidosis / Sarcoidosis

La sarcoidosis es una enfermedad granulomatosa sistémica caracterizada por la presencia histológica de granulomas no caseificantes. En este trabajo se ofrece una panorámica general de la enfermedad, su historia, hipótesis etiológicas, patología, inmunología y genética, cuadro clínico general y clasificación, dificultades diagnósticas y utilidad de los exámenes disponibles en la actualidad, evolución y forma de seguimiento. Por último, se expone el tratamiento con el esquema utilizado por uno de los Centros de mayor estudio de esta patología y el lugar que ocupan las drogas de segunda línea

HLA association with sarcoidosis and diffuse interstitial pulmonary fibrosis.

HLA typing was performed on 18 patients suffering from sarcoidosis and 30 patients suffering from diffuse interstitial pulmonary fibrosis. One hundred normal healthy people ethnically matched served as the controls. On statistical analysis, the corrected 'p' value of all the HLA antigens for both the patient groups was non significant. The results therefore suggest that there is no particular HLA antigen associated with sarcoidosis and diffuse interstitial pulmonary fibrosis.

Blood helper/suppressor lymphocyte ratio in sarcoidosis.

The blood helper/suppressor ratio was measured in 38 patients with biopsy-proved sarcoidosis. There was no relationship between this peripheral helper/suppressor ratio and the activity of the granulomatous process. This test needs further evaluation before its routine use in assessing activity in sarcoidosis.