Patogênese da síndrome pulmonar hemorrágica na leptospirose humana / Pathogenesis of leptospirosis pulmonary hemorrhage syndrome in human

AUTOR(ES)
DATA DE PUBLICAÇÃO

2008

RESUMO

Leptospirosis is a zoonotic disease that is a cause of high morbidity and mortality in humans and is an important public health problem. Caused by bacteria of Leptospira genus, this disease presents diverse clinical manifestations and is especially important in developing countries. Leptospirosis pulmonary hemorrhage syndrome is the major cause of death in patients with the severe form of leptospirosis. The pathogenic mechanisms of this syndrome are unknown. With the purpose of identifying these pathogenic mechanisms, 30 necropsies (pulmonary samples) from patients with leptospirosis pulmonary hemorrhage syndrome and seven controls were evaluated. . To determine whether the immune system is involved, histology and immunohistochemistry (IgM, IgG, IgA, and C3) experiments were performed on lung tissue samples, as well sera measurements of autoantibodies (against the basal membrane and anti-cardiolipin) were performed in leptospirosis patients with and without pulmonary hemorrhage syndrome (in paired samples) and in healthy donors from a blood bank. We found that patients with leptospirosis pulmonary hemorrhage syndrome differed from control pulmonary hemorrhage patients in several features: the presence of moderate to high levels of macrophages in the alveolar space (77% versus 29%, respectively; p = 0.02), the presence of the focal hyaline membrane on alveolar surface (100% versus 0%; p <0.01), extensive necrosis and regeneration of pneumocyte II cells (100% versus 0%; p <0.01) and the presence of plasma cells in the alveolar septum (77% versus 29%, respectively; p =0.02). No statistically significant differences were observed in the number of others cells in the alveolar septae. Intact leptospires were rarely detected. Leptospiral antigen was not correlated with the intensity of the lesions. None of the patients showed microscopic evidence for disseminated intravascular coagulation. Immunoglobulin deposits were detected on the alveolar surface of 18/30 leptospirosis patients with pulmonary hemorrhage. Three staining patterns were observed for the immunoglobulins and C3 in the lung tissues of leptospirosis patients with pulmonary hemorrhage syndrom: (A) delicate linear staining adjacent to the alveolar surface, like a membrane covering the luminal surface of type I and II pneumocyte cells; (MF) random, multifocal staining along the alveolar septum; and (I) weak, focal intra-alveolar granular staining.. We were not able to show any significant difference in autoantibodies concentration in the different groups. We found significant difference between the titles of anticardiolipin IgM antibodies in the first and second sera sample from leptospirosis patients with and without pulmonary hemorrhage (p<0.01 e p=0.04, respectively). The increased in the titles of anti-cardiolipin IgG antibodies, as well IgG/IgM ratio was observed only in patients with pulmonary hemorrhage(p=0.01 and p=0.01). We concluded that the pulmonary involvement on severe human leptospirosis have particular characteristics, which the morphologic aspect differ from the others causes of lung hemorrhage. It was distinguished by linear deposition of immunoglobulin and complement (C3C) on the luminal alveolar surface of pneumocyte I and II cells. This event was associated with pneumocyte I and II cells necrosis, pneumocyte II regeneration and septal and alveolar inflammation

ASSUNTO(S)

respiratory insufficiency insuficiência respiratória autopsy imunoglobina a hantavirus pulmonary syndrome autopsia leptospirose/etiologia leptospirosis/ethnology sindrome pulmonar por hantavírus

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