Nivolumab and interferon-γ rescue therapy to control mixed mould and bacterial superinfection after necrotizing fasciitis and septic shock

Immunosuppression is a major feature of septic shock and patients are at increased risk for opportunistic infections. We describe a successful use of immunostimulation to treat mixed mould and bacterial superinfection in a previously healthy 38-year-old female patient admitted for severe extensive fasciitis. Interferon gamma associated with nivolumab reversed successfully deactivation of immune cells assessed by altered expressions of monocyte human leukocyte antigen-DR (HLA-DR) and lymphocyte programmed death receptor-1 (PD-1). Immunosuppressed patients in ICU with invasive bacterial and fungal infections may benefit from immunostimulation

Morbi-mortalité du polytraumatisme chez les patients très âgés

International audienc

Integrated clustering of multiple immune marker trajectories reveals different immunotypes in severely injured patients

International audienceAbstract Background The immune response of critically ill patients, such as those with sepsis, severe trauma, or major surgery, is heterogeneous and dynamic, but its characterization and impact on outcomes are poorly understood. Until now, the primary challenge in advancing our understanding of the disease has been to concurrently address both multiparametric and temporal aspects. Methods We used a clustering method to identify distinct groups of patients, based on various immune marker trajectories during the first week after admission to ICU. In 339 severely injured patients, we initially longitudinally clustered common biomarkers (both soluble and cellular parameters), whose variations are well-established during the immunosuppressive phase of sepsis. We then applied this multi-trajectory clustering using markers composed of whole blood immune-related mRNA. Results We found that both sets of markers revealed two immunotypes, one of which was associated with worse outcomes, such as increased risk of hospital-acquired infection and mortality, and prolonged hospital stays. This immunotype showed signs of both hyperinflammation and immunosuppression, which persisted over time. Conclusion Our study suggest that the immune system of critically ill patients can be characterized by two distinct longitudinal immunotypes, one of which included patients with a persistently dysregulated and impaired immune response. This work confirms the relevance of such methodology to stratify patients and pave the way for further studies using markers indicative of potential immunomodulatory drug targets. Graphical Abstrac

PD-L1⁺ plasma cells suppress T lymphocyte responses in patients with sepsis and mouse sepsis models

International audienceSepsis, a leading cause of death in intensive care units, is associated with immune alterations that increase the patients’ risk of secondary infections and mortality, so better understandings of the pathophysiology of sepsis-induced immunosuppression is essential for the development of therapeutic strategies. In a murine model of sepsis that recapitulates immune alterations observed in patients, here we demonstrate that PD-L1+ CD44+B220LowCD138+IgM+ regulatory plasma cells are induced in spleen and regulate ex vivo proliferation and IFNɣ secretion induced by stimulation of T splenocytes. This effect is mediated both by cell-cell contact through increased PD-L1 expression on plasma cells and by production of a soluble factor. These observations are recapitulated in three cohorts of critically ill patients with bacterial and viral sepsis in association with increased mortality. Our findings thus reveal the function of regulatory plasma cells in the pathophysiology of sepsis-induced immune alterations, and present a potential therapeutic target for improving immune cell function impaired by sepsis