Plasma proteome analysis in sepsis

BEATRIZ LÓPEZ; ISTURIZ MARTÍN A.; JOHANA MONTESERIN; NORBERTO SÍMBOLI; DANIELA MONTAGNA; ROXANA PAUL; NOEMÍ YOKOBORI; BÁRBARA REARTE; MAURICIO SANTOS; MÓNICA PRIETO; MARÍA FLORENCIA TODERO

CABA

Exposici�n; DRAGONS' DEN at the 18th ICID / XVIII SADI; 2017

International Society for Infectious Diseases (ISID /Sociedad Argentina de Infectologia (SADI)

There is an increasing awareness of the biphasic nature of sepsis, where an exacerbated proinflammatory response is followed by a later phase dominated by immunosuppression, when most deaths occur. In this context, specific interventions to enhance the immune response were proposed, but clinicians lack an accurate tool to stratify septic patients for decision making. More than 150 failed clinical trials for potential treatments and over 180 biomarkers tested with unsatisfactory results in sepsis unveil its complex nature. The dynamism of sepsis demands tools that can quickly guide clinicians about the patient?s immune state. However, no single biomarker has proven to be powerful enough, and probably will never be. Combinations of biomarkers have shown to improve their performance, but for immunoassay-based tests this would lead to higher costs. Moreover, these assays can be too time consuming considering the vertiginous development of the different phases in sepsis. MALDI-TOF based biotyping is transforming the clinical microbiology lab, due to its high cost-effectiveness: it is simple, quick, cheap and accurate. For these reasons, this technology is quickly spreading into many health care centers, even in middle to low income settings. Our proposal is to generate plasma proteomic fingerprints, simultaneously analyzing a spectrum of markers that can be detected by MALDI-TOF. If proved to be successful, MALDI-based plasma spectra would be: 1) quick: spectra could be obtained within minutes; 2) cheap: the only consumable needed is the HCCA matrix; 3) objective: spectra would be analyzed by computational algorithms; 4) non-invasive: blood tests are routinely performed in critical patients; 5) methodologically simple; 6) feasible and scalable due to the spread of MALDI-TOF-based biotyping in clinical settings. We are developing a proof of concept test with plasma collected in a murine model of sepsis, with promising results.