Dados do Trabalho

Título

ACTIVATION OF THE COMPLEMENT SYSTEM IN PATIENTS WITH PULMONARY HEMORRHAGIC SYNDROME ASSOCIATED WITH HUMAN LEPTOSPIROSIS

Introdução

Leptospirosis is a neglected zoonosis, endemic in developing countries with tropical or subtropical climates. Approximately one million new cases are reported yearly with 5-10 deaths. Some patients develop a clinical condition called Leptospirosis-associated Severe Pulmonary Hemorrhagic Syndrome (LPHS), with a mortality rate higher than 50%. The etiopathology of LPHS remains to be elucidated. Some evidence suggests that its progression is multifactorial and may be due to: (1) leptospiral toxins that can damage blood capillaries, affect vascular permeability, and allow the entry of a high number of bacteria into the tissues; and (2) an exacerbated immune response, causing a significant release of cytokines and anaphylatoxins that can affect tissue permeability, cause tissue damage and local hemorrhage. The deposition of C3 in the lungs of patients with LPHS has been previously reported, in human and animal models, suggesting that the activation of the Complement System may contribute to the hemorrhagic clinical picture. However, the role of the Complement System in LPHS still needs to be further investigated.

Objetivo (s)

Evaluate the possible activation of the Complement System in patients who died from LPHS and identify the pathways involved in this process.

Material e Métodos

Samples from dead LPHS patients (n=11) were used and compared to patients who died of sepsis (n=4) and cardiopathies (n=6). Histopathological analysis was carried out in the lungs, kidneys, and liver of the 3 groups. Immunohistochemical assays were performed to analyze the deposition of Complement proteins: C1q, Factor B, MASP2, C3c, C4d, C5b-9 and the presence of anaphylatoxin receptors C3aR1 and C5aR, in the 3 study groups. At the same time, immunoglobulins (IgG and IgM) deposition in the tissue and Leptospira antigens were evaluated.

Resultados e Conclusão

In the LPHS group, the lungs were observed to have a higher intensity of the hemorrhagic condition and a higher incidence of septal inflammation. In the liver, moderate and intense dissociation of hepatocyte levels, lobular and portal inflammation were observed. Furthermore, there was a higher presence of tubular injury and mesangial hyperplasia in the kidneys when compared to the controls. The pulmonary analysis revealed a higher deposition of C1q in the alveolar septum of LPHS patients, suggesting an activation of the Classical Pathway. We believe that understanding the contribution of Complement in LPHS can guide the future use of inhibitors as a treatment for patients.

Palavras Chave

leptospira; Leptospirose; Sistema Complemento; Hemorragia Pulmonar