Estudo das micropartículas derivadas de células na endocardite infecciosa

Abstract

INTRODUCTION: Infectious endocarditis (IE) is a serious disease, with high rates of morbidity and mortality. IE evolution are determined by complex processes, such as pathogen-host interaction, establishment of a pattern of immune and inflammatory response, as well as cellular activation. Recently, a growing number of scientific studies have demonstrated the participation of cell-derived microparticles (MPs) in these processes. However, to date, there are no studies evaluating MPs in IE, both at diagnosis and during treatment, and its relation to clinical outcomes. The present study was designed to evaluate the serum levels of MPs derived from leukocytes, neutrophils, monocytes, T lymphocytes, endothelial cells, erythrocytes and platelets in patients with IE. The profile of MPs was analyzed during treatment to determine the impact of these new markers on clinical outcomes, defined as the need for early surgery and in-hospital death, the development of heart failure and stroke. In addition, the concentration of MPs in IE was compared with other bacterial infections. METHODS: Between August 2011 and January 2017, 57 patients with probable or definite IE according to the modified Duke criteria hospitalized at the Hospital das Clínicas of UFMG were included. The patients were followed up during the hospitalization with clinical, laboratory and echocardiographic data collection. Plasma samples were obtained at three times: at hospital admission (T0), after two weeks of treatment (T1) and at the end of treatment (T2). Patients with IE were compared to a control group composed of 22 patients with other bacterial infections, characterized by fever and elevated C-reactive protein (CRP). MPs were measured by flow cytometry, using annexin as a universal marker and labeled antibodies directed to specific cell antigens: CD45 (leukocytes), CD66b (neutrophils), CD14 (monocytes), CD41a (platelets), CD51 (endothelial cells) and CD235a (erythrocytes). The patients were treated according to the recommendations of the guidelines and the surgical indication was based on criteria well established in the literature. RESULTS: The median age of the patients was 50 years, with 33 male patients (58%). The most frequent predisposing condition was rheumatic heart disease, detected in 30% of the cases. The most prevalent microorganisms were staphylococcus (37%), followed by streptococcus (12%). In 17 patients (30%), blood culture was negative. Platelet MPs (pltMPs), leukocytes (leukMPs), neutrophils (neutMPs), and T lymphocytes (lympMPs) were significantly elevated in patients with IE compared to patients with other bacterial infections despite age, sex, global leukocyte and protein C reactive. By evaluating the MPs kinetics during the treatment, we observed that the MPs values had a relatively stable pattern over time, except for a significant increase of leukMPS and neutMPs between T0 and T1. During hospital stay, 17 patients died (30%), 25 needed heart surgery (44%), 29 had heart failure (51%) and 9 had a stroke (16%). Regarding the outcomes, leukMPs, neutMPs, lymphMPs and MPs of monocytes (monoMPs), measured at admission, were significantly elevated in patients with IE who died during hospitalization compared to patients who survived. There was no difference in MP levels, comparing patients who required cardiac surgery with the ones on clinical treatment, or those who developed heart failure or not, or that complicated or not with stroke. In a multivariate analysis, neutMPs levels remained an independent factor associated with mortality (OR 2.2 for each increase of 100 counts/μL, 95% confidence interval 1.2 to 4, p = 0.009) CONCLUSIONS: Plasma concentrations of MPs of leukocytes, neutrophils, T lymphocytes and platelets were significantly elevated in patients with IE when compared to other bacterial infections. Except for the significant elevation of MPs derived from neutrophils, MP levels presented a relatively stable pattern throughout the three evaluated times. MPs derived from leukocytes, including neutrophils, monocytes, and lymphocytes, were elevated in patients who died during hospitalization. The MPs present a potential value in IE, aiding in the differential diagnosis with other bacterial infections and useful in the identification of patients with higher risk of death.