HANTAVIRUS INDUCED CHANGES IN T-CELL SUBPOPULATIONS AND SHOWED UP-REGULATION OF PRO-INFLAMMATORY CYTOKINES RELATED WITH DISEASE SEVERITY

IGLESIAS AYELÉN; GARCIA MARINA; PERIOLO NATALIA,; ALONSO DANIEL; SHIERLOH PABLO; MARTINEZ VALERIA

Congreso; Reunión Conjunta de las Sociedades Biomédicas; 2017

Hantaviruses are emerging human pathogens. These zoonotic viruses are responsible of two different clinical presentations, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Hantaviruses predominantly infect microvascular endothelial cells causing capillary leakage. The hallmark of hantavirus diseases is the vascular permeability, which leads to pulmonary edema in HPS patients. HPS is endemic in Argentina where it was associated to high case fatality rates. In order to evaluate the role of the immune response on pathogenesis we performed cytokine profile analysis and initial T-cell phenotypic characterization in HPS patients.For biomarkers analysis we study 109 HPS patients including 39 dead patients (D) and 69 survivors (S). Control samples were obtained from healthy adult volunteers (HV). Serum cytokine and granzyme levels were analyzed using multiplex magnetic bead-based technology by a Luminex 200 analyzer. Fresh blood samples were collected to analyze surface markers on T cell subpopulations by flow cytometry in 19 patients. Statistical analysis was performed by Student?s t-test using GraphPad Prism 6 software. We found significant higher levels of IL-2, IL-4, IL-6, IL-8, IL-10, INF-γ, GM-CSF and TNFα in patients compared with HV. Interestingly, we showed an increased of Granzyme A and B in patient´s sera compared with HV. Analysis of T cells subsets in patients showed increase in CD8+ cells, resulting in the inversion of the CD4/CD8 ratio compared to HV. This preliminary phenotypic analysis of T cell subpopulations showed an increase of CD38+ /CD27- in CD4+ and decrease in CD28, CD27 and CD127 in CD3+/CD8+ cells. In addition to this, we observed high number of classic monocytes (CD14+CD16+) in patients compared with HV. Our results showed a differential biomarker expression according to disease severity. This, together with the preliminary T cell analysis, would suggest an active role of immune response in pathogenesis.